参芪复方对GK大鼠大血管病变血管紧张素Ⅱ及其受体影响的实验研究
|
摘要
目的：通过对糖尿病GK大鼠使用具有益气养阴、活血化瘀的参芪复方,从.基因水平、分子水平及整体水平来评价参芪复方对实验大鼠的治疗效果。从血管紧张素及其受体的角度来说明参芪复方防治糖尿病大血管病变的机制。
方法：73只糖尿病GK大鼠随机分为4组：GK组18只、模型组19只、西药阿托伐他汀组18只、中药参芪复方组18只,同时予Wistar大鼠18只作为正常对照组。其中模型、西药及中药三组予以内皮型一氧化氮合成酶(eNOS)抑制剂Nω-硝基-L-精氨酸甲酯(L-NAME 0.1mg·ml-1·d-1)加入饮用水中进行造模,造模时间为35天。Wistar对照组用普通饲料饲养,其余各组均用高脂饲料饲养。造模的同时开始给药,Wistar对照组按照5ml·kg1·d-1灌服生理盐水,GK组按照5ml·kg-1·d-1灌服生理盐水,模型组按照5ml·kg-1·d-1灌服生理盐水,西药组按照1.6mg·kg-1·d-1灌服阿托伐他汀钙悬液,中药组按照1.44g·kg-1·d-1灌服参芪复方混悬液。35天后处死大鼠,检测各组血糖、血脂、血清C反应蛋白(CRP)及血清血管紧张素Ⅱ(AngⅡ);利用免疫组化技术测定大鼠腹主动脉血管紧张素Ⅱ1型受体(AT1R)和血管紧张素Ⅱ2型受体(AT2R)的积分光密度值；用实时荧光定量聚合酶链反应(RT-PCR)技术检测大鼠腹主动脉血管紧张素Ⅱ1型受体信使核糖核酸(AT1RmRNA)的表达量；用免疫印迹法测定细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)在胸主动脉的表达。
结果：通过光镜观察主动脉病理形态,模型组呈现典型动脉粥样硬化病理改变,其血糖、总胆固醇(TC)、甘油三酯(TG)、CRP及AngⅡ水平明显高于其他四组(P<0.05或P<0.01)。参芪复方治疗可以促进糖尿病大血管病GK大鼠的体重增长,降低血糖水平,降低血清TC、TG、CRP及AngⅡ水平；可以降低大鼠主动脉血管壁中AT1RmRNA的表达,减少AT1R蛋白的合成,增加AT2R蛋白的合成；参芪复方还可以减少主动脉中ICAM-1和VCAM-1蛋白的含量。
结论：参芪复方可以改善糖尿病大血管病变GK大鼠生长发育,改善其糖、脂代谢,减轻炎症反应,延缓糖尿病动脉粥样硬化的进展。而降低血清AngⅡ水平,抑制主动脉血管壁AT1RmRNA表达及AT1R蛋白合成,增加AT2R蛋白的合成可能是参芪复方治疗糖尿病大血管病变的机制之一。
Objective:To elvaluate the therapeutic effect of ShenQi compound recipe(SQCR) on the diabetes mellitus macrovasculopathy GK rat,which has the function of tonifying Qi and Yin and promoting blood circulation to dissipate stasis,in the level of gene, molecular and cell leve.To demonstrate the mechanism of SQCR for diabetes mellitus macrovasculopathy from the view of angiotensin and its recepors.
Methods:73 GK male rats were divided into four groups randomly:respectively 18 in GK group, drenched normal saline 5ml·kg-1·d-1,19 in model group, drenched normal saline 5ml·kg-1·d-1,18 in atorvastatin groups, drenched atorvastatin calcium suspension 1.6mg·kg-1·d-1,18 in SQCR group, drenched SQCR suspl 1.44g·kg-1·d-1. 18 SPF Wistar rats in the control group was drenched normal saline 5ml·kg-1·d-1. In order to build the diabetes mellitus macroangiopathy model, the model, atorvatatin, SQCR groups were administered with the Nω-nitro-L-arginine methyl ester(L-NAME) 0.1mg·ml-1·d-1 in the drinking water for 35 days. After sacrifice, detect the blood glucose, blood fat, blood secum C reactive protein (CRP) and AngiotensinⅡ;dectect the angiotensinⅡtype 1 receptor(AT1R)mRNA expression in the abdominal aorta vessel wall by real-time PCR; dectect the integral optical density of AT1R and AT2R in the abdominal aorta vessel wall by immunohistochemistry;detect the intercellular adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) by western blot.
Result:The typical atheromatosis pathoalteration was observed in model group by light microscope in arteriae aorta appearance. Compared with other groups, the blood glucose, fat, CRP and AngⅡraised up in model groups (P<0.05 or P<0.01). Increased body weight, degraded blood glucose, fat, CRP and AngⅡand relieved inflammatory reaction was observed in the GK rats treated by SQCR. in addition, the SQCR can also downregulate the AT1RmRNA expression, decrease the synthesis of AT1R, enhance the AT2R, decrease the ICAM-1 and VCAM-1 in abdominal aorta vessel wall.
Conclusion:SQCR could delay the development of diabetes mellitus AS by improving the growth, gaining weight, depressing blood glucose and blood fat, degrading blood CRP and AngⅡ.One of the possible treatment mechanisms in molecular biology is to decrease the AngⅡin the surem,downregulate the expression of AT1RmRNA and synthesis of AT1R,and increase the synthesis of AT2R in vessel wall.
方法：73只糖尿病GK大鼠随机分为4组：GK组18只、模型组19只、西药阿托伐他汀组18只、中药参芪复方组18只,同时予Wistar大鼠18只作为正常对照组。其中模型、西药及中药三组予以内皮型一氧化氮合成酶(eNOS)抑制剂Nω-硝基-L-精氨酸甲酯(L-NAME 0.1mg·ml-1·d-1)加入饮用水中进行造模,造模时间为35天。Wistar对照组用普通饲料饲养,其余各组均用高脂饲料饲养。造模的同时开始给药,Wistar对照组按照5ml·kg1·d-1灌服生理盐水,GK组按照5ml·kg-1·d-1灌服生理盐水,模型组按照5ml·kg-1·d-1灌服生理盐水,西药组按照1.6mg·kg-1·d-1灌服阿托伐他汀钙悬液,中药组按照1.44g·kg-1·d-1灌服参芪复方混悬液。35天后处死大鼠,检测各组血糖、血脂、血清C反应蛋白(CRP)及血清血管紧张素Ⅱ(AngⅡ);利用免疫组化技术测定大鼠腹主动脉血管紧张素Ⅱ1型受体(AT1R)和血管紧张素Ⅱ2型受体(AT2R)的积分光密度值；用实时荧光定量聚合酶链反应(RT-PCR)技术检测大鼠腹主动脉血管紧张素Ⅱ1型受体信使核糖核酸(AT1RmRNA)的表达量；用免疫印迹法测定细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)在胸主动脉的表达。
结果：通过光镜观察主动脉病理形态,模型组呈现典型动脉粥样硬化病理改变,其血糖、总胆固醇(TC)、甘油三酯(TG)、CRP及AngⅡ水平明显高于其他四组(P<0.05或P<0.01)。参芪复方治疗可以促进糖尿病大血管病GK大鼠的体重增长,降低血糖水平,降低血清TC、TG、CRP及AngⅡ水平；可以降低大鼠主动脉血管壁中AT1RmRNA的表达,减少AT1R蛋白的合成,增加AT2R蛋白的合成；参芪复方还可以减少主动脉中ICAM-1和VCAM-1蛋白的含量。
结论：参芪复方可以改善糖尿病大血管病变GK大鼠生长发育,改善其糖、脂代谢,减轻炎症反应,延缓糖尿病动脉粥样硬化的进展。而降低血清AngⅡ水平,抑制主动脉血管壁AT1RmRNA表达及AT1R蛋白合成,增加AT2R蛋白的合成可能是参芪复方治疗糖尿病大血管病变的机制之一。
Objective:To elvaluate the therapeutic effect of ShenQi compound recipe(SQCR) on the diabetes mellitus macrovasculopathy GK rat,which has the function of tonifying Qi and Yin and promoting blood circulation to dissipate stasis,in the level of gene, molecular and cell leve.To demonstrate the mechanism of SQCR for diabetes mellitus macrovasculopathy from the view of angiotensin and its recepors.
Methods:73 GK male rats were divided into four groups randomly:respectively 18 in GK group, drenched normal saline 5ml·kg-1·d-1,19 in model group, drenched normal saline 5ml·kg-1·d-1,18 in atorvastatin groups, drenched atorvastatin calcium suspension 1.6mg·kg-1·d-1,18 in SQCR group, drenched SQCR suspl 1.44g·kg-1·d-1. 18 SPF Wistar rats in the control group was drenched normal saline 5ml·kg-1·d-1. In order to build the diabetes mellitus macroangiopathy model, the model, atorvatatin, SQCR groups were administered with the Nω-nitro-L-arginine methyl ester(L-NAME) 0.1mg·ml-1·d-1 in the drinking water for 35 days. After sacrifice, detect the blood glucose, blood fat, blood secum C reactive protein (CRP) and AngiotensinⅡ;dectect the angiotensinⅡtype 1 receptor(AT1R)mRNA expression in the abdominal aorta vessel wall by real-time PCR; dectect the integral optical density of AT1R and AT2R in the abdominal aorta vessel wall by immunohistochemistry;detect the intercellular adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) by western blot.
Result:The typical atheromatosis pathoalteration was observed in model group by light microscope in arteriae aorta appearance. Compared with other groups, the blood glucose, fat, CRP and AngⅡraised up in model groups (P<0.05 or P<0.01). Increased body weight, degraded blood glucose, fat, CRP and AngⅡand relieved inflammatory reaction was observed in the GK rats treated by SQCR. in addition, the SQCR can also downregulate the AT1RmRNA expression, decrease the synthesis of AT1R, enhance the AT2R, decrease the ICAM-1 and VCAM-1 in abdominal aorta vessel wall.
Conclusion:SQCR could delay the development of diabetes mellitus AS by improving the growth, gaining weight, depressing blood glucose and blood fat, degrading blood CRP and AngⅡ.One of the possible treatment mechanisms in molecular biology is to decrease the AngⅡin the surem,downregulate the expression of AT1RmRNA and synthesis of AT1R,and increase the synthesis of AT2R in vessel wall.
引文
[1]WHO.Diabetes Action Now Booklet.A life-threatening Condition.Available at http://www.who.int/diabetes/BOOKLET_HTML/en/index3.html(accessed 19 September 2005.
[2]卫生部疾病控制司,中华医学会糖尿病学分会.《中国糖尿病防治指南》试行本节选[J].中国慢性病预防与控制,2004,12(6)：283-285.
[3]Kanaya AM,Grady D,Barrett-Connor E.Explaining the sex difference in coronary heart disease mortality among patients with type 2 diabetes mellitus:a meta-analysis[J].Arch Intern Med,2002,162(15):1737-45.
[4]American Diabetes Association.Economic consequences of diabetes mellitus in the U.S. in 1997[J].Diabetes Care,1998,21(2):296-309.
[5]Fiordaliso F,Li B,Latini R,et al.Myocyte death in streptozotocin-induced diabetes in rats in angiotensin Ⅱ-dependent[J].Lab Invest,2000,80(4):513-517.
[6]Kajstura J,Fiordaliso F,Andreoli AM,et al.IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and angiotensin Ⅱ-mediated oxidative stress[J].Diabetes,2001,50(6):1414-1424.
[7]全国糖尿病研究协作组调查研究组.全国14省市30万人口中糖尿病调查报告[J].中华内科杂志,1981,20(11)：678-83.
[8]Pan XR,Yang WY,Liu J.Prevalence of diabetes and its risk factors in China,1994[J].National Diabetes Prevention and Control Cooperative Group.Diabetes Care,1997,20(11):1664-9.
[9]http://www.eatlas.idf.org/Prevalence/.
[10]中华医学会糖尿病学分会慢性并发症调查组.1991-2000年全国住院糖尿病患者慢性并发症及相关大血管病变回顾性分析[J].中国医学科学院学报,2002,24(5)：447-51.
[11]田代华整理.黄帝内经素问[M].北京：人民卫生出版社,2005：59.
[12]田代华整理.黄帝内经素问[M].北京：人民卫生出版社,2005：116.
[13]汉·张仲景著,何任,何若苹整理.金匮要略[M].北京：人民卫生出版社,2005：50.
[14]明·戴原礼撰,王英,江凌圳,竹剑平整理.秘传证治要诀及类方[M].北京：人民卫生出版社,2006：85.
[15]明·张介宾撰,李继明王大涥等整理.景岳全书[M].北京：人民卫生出版社,2005：422.
[16]田代华整理.黄帝内经素问[M].北京：人民卫生出版社,2005：93.
[17]田代华,刘更生整理.灵枢经[M].北京：人民卫生出版社,2005：97-98.
[18]宋·赵佶编.圣济总录[M].北京：人民卫生出版社,1982：1064-1099.
[19]许敬生主编.罗天益医学全书[M].北京：中国中医药出版社,2006：101.
[20]田代华整理.黄帝内经素问[M].北京：人民卫生出版社,2005：15.
[21]田代华,刘更生整理.灵枢经[M].北京：人民卫生出版社,2005：95.
[22]清·叶天士撰,苏礼,焦振廉等整理.临证指南医案[M].北京：人民卫生出版社,2005：271.
[23]唐·王焘撰,外台秘要[M].北京：人民卫生出版社,1982：306.
[24]汉·张仲景著,何任,何若苹整理.金匮要略[M].北京：人民卫生出版社,2005：51.
[25]宋·王怀隐等编.太平圣惠方[M].北京：人民卫生出版社,1982：1624.
[26]宋乃光主编.刘完素医学全书[M].北京：中国中医药出版社,2006：274.
[27]明·李梃原著,田代华,金丽,何永点校.医学入门[M].天津：天津科学技术出版社,2000：880.
[28]明·张介宾撰,李继明王大涥等整理.景岳全书[M].北京：人民卫生出版社,2005：423-424.
[29]清·叶天士撰,苏礼,焦振廉等整理.临证指南医案[M].北京：人民卫生出版社,2005：272.
[30]中国中西医结合学会糖尿病专业委员会.中西医结合糖尿病诊疗标准(草案)[J].中国中西医结合杂志,2005,25(1)：94-95.
[31]林兰.现代中医糖尿病学[M].北京：人民卫生出版社,2008：737.
[32]梁平茂,曹克光.2型糖尿病血管并发症中医病机探讨[J].中医杂志,2006,47(10)：726.
[33]李振中,尹翠梅.痰浊瘀血与糖尿病血管病变理论探讨[J].中西医结合心脑血管病杂志,2005,3(11)：983-985.
[34]李步满,吴深涛,吴丽丽.2型糖尿病血管并发症与“阴火”病机的相关性探讨[J].辽宁中医杂志,2007,34(9)：1229-1231.
[35]王苢生,赵文景,夏军,等.益气养阴活血方对气阴两虚血瘀型糖尿病患者血浆内皮素与一氧化氮水平的影响[J].中国中西医结合杂志,2000,20(8)：571-573.
[36]Creager MA,Luscher TF, Cosentino F,et al.Diabetes and vascular disease:pathophysiology,clinical consequences and medical therapy:part I [J].Circulation,2003:108[12]:1655-1661.
[37]Luscher TF,Creager MA,Beckman JA,et al.Diabetes and vascular disease:pathophysiology,clinical consequences and medical therapy:part II [J].Circulation,2003:108(13):1527-1532.
[38]Beckman JA.Pathophysiology of vascular dysfunction in diabetes[J].Cardiology Rounds,2004,8(10):1-5.
'[39]Kadirvelu A,Han CK,Lang CC.Endothelial dysfunction in cardiovascular diseases[J].Med Prog,2002,May:4-10.
[40]Drexler H,Hornig B.Endothelial dysfunction in human disease[J].J Mol Cell Cardiol,1999;31(1):51-60.
[41]van der Loo B,Labugger R,Skepper JN,et al.Enhanced peroxynitrite formation is associated with vascular aging[J].J Exp Med,2000,192:1731-1744.
[42]Taylor PD,Poston L.The effect of hyperglycaemia on function of rat isolated mesenteric resistance artery[J].Br J Pharmacol,1994; 113:801-808.
[43]Tooke JE.Microvascular function in human diabetes. A physiological perspective[J].Diabetes,1995;44(7):721-726.
[44]Rattan V,Sultana C,Shen Y,et al.Oxidant stress-induced transendothelial migration of monocytes is linked to phosphorylation of PEC AM-1[J]. Am J Physiol,1997;273(3 pt 1):E453-E461.
[45]Tesfamariam B,Brown ML,Cohen RA.Elevated glucose impaires endothelium-dependent relaxation by activating protein kinase C[J].J Clin Invest,1991;87(5):1643-1648.
[46]Poston L,Taylor PD.Glaxo/MRS Young Investigator Prize.Endothelium-mediated vascular function in insulin-dependent diabetes mellitus[J].Clin Sci(Lond),1995,88(3):245-255.
[47]Furchgott RF,Zawadzki JV.The obligatory role of the endothelial cells in the relaxation of arterial smooth muscle by acetylcholine[J].Nature,1980,288(5789):373-376.
[48]Cines DB,Pollak ES,Buck CA,et al.Endothelial cells in physiology and in the pathophysiology of vascular disorders[J].Blood,1998,91(10):3527-3561.
[49]Storey AM,Perry CJ,Petrie JR.Endothelial dysfunction in Type 2 diabetes[J].Br J Diabetes Vasc Dis,2001,1(1):22-27.
[50]Baynes JW.Role of oxidative stress in development of complication in diabetes[J].Diabetes,1991,40(4):405-412.
[51]Morigi M,Angioletti S,Imberti B,et al.Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-K B-dependent fashion[J].J Clin Invest,1998,101(9):1905-1915.
[52]Cagliero E,Roth T,Roy S,et al.Characteristics and mechanisms of high-glucose-induced overexpresssion of basement membrane components in cultured human endothelial cells[J].Diabetes,1991,40(1):102-110.
[53]Vlassara H.Recent progress in advanced glycation end products and diabetic complications[J].Diabetes,1997,46(Suppl.2):S 19-S25.
[54]Lyons TJ.Glycation and oxidation:a role in the pathogenesis of atherosclerosis[J].Am J Cardiol,1993,71(6):26B-31B.
[55]Beckman JA,Creager MA,Libby P.Diabetes and atherosclerosis:epidemiology,pathophysiology,and management[J].JAMA,2002,287(19):2570-2581.
[56]Taguchi S,Oinuma T,Yamada T.A comparative study of cultured smooth muscle cell proliferation and injury,utilizing glycated low density lipoproteins with slight oxidation,auto-oxidation,or extensive oxidation[J].J Atheroscler Thromb,2000,7(3):132-137.
[57]Chaturvedi N,Fuller JH,Pokras F,et al.Circulating plasma vascular endothelial growth factor and microvascular complications of type 1 diabetes mellitus:the influence of AGE inhibition[J].Diabet Med,2001,18(4):288-294.
[58]Walsh MF,Dominguez LJ, Sowers JR.Metabolic abnormalities in cardiac ischemia[J].Cardiol Clin,1995,13(4):529-538.
[59]Davi QCatalano I,Averna M,et al.Thromboxane biosynthesis and platelet function in type Ⅱ diabetes mellitus[J].N Engl Med,1990,322(25):1768-1774.
[60]Winocour PD,Bryszewska M,Watala C,et al.Reduced membrane fluidity in platelets from diabetic patients[J].Diabetes,1990,39(2):241-244.
[61]Standley PR,Ali S,Bapna C.Increased platelet cytosolic calcium responses to low density lipoprotein in type Ⅱ diabetes with and without hypertension[J].Am J Hypertens,1993,6(11 pt 1):938-943.
[62]Levy J,Gavin JR Ⅲ,Sowers JR.Diabetes mellitus:a disease of abnormal cellular calcium metabolism?[J].Am J Med,1994; 96(3):260-273.
[63]Fukuda K,Ozaki Y,Satoh K,et al.Phosphorylation of myosin light chain in resting platelets from NIDDM patients is enhanced:correlation with spontaneous aggregation[J].Diabetes,1997,46(3):588-593.
[64]Vinik AI,Erbas T,Park TS,et al.Platelet dysfunction in type 2 diabetes[J].Diabetes Care,2001,24(8):1476-1485.
[65]Sampietro T,Lenzi S,Cecchetti P,et al.Nonenzymatic glycation of human platelet membrane proteins in vitro and in vivo[J].Clin Chem,1986,32(7):1328-1331.
[66]Myllarniemi M,Calderon L,Lemstrom K,et al.Inhibition of platelet-derived growth factors receptor kinase inhibits vscular smooth muscle cell migration and proliferation[J].FASEB J,1997,11(13):1119-1126.
[67]Okuda Y,Adrogue HJ,Nakajima T,et al.Increased production of PDGF by angiotensin and high glucose in human vascular endothelium[J].Life Sci,1996,59(17):1455-1461.
[68]Jokl R,Colwell JA.Arterial thrombosis and atherosclerosis in diabetes[J].Diabetes Metab Rev,1997; 5:1-15.
[69]Tschoepe D,Rauch U,Schwippert B.Platelet-leukocyte-cross-talk in diabetes mellitus[J].Horm Metab Res,1997,29(12):631-635.
[70]Li Y,Woo V,Bose R.Platelet hyperactivity and abnormal Ca(2+) homeostasis in diabetes mellitus[J].Am J Physiol Heart Circ Physiol,2001,280(4):H1480-H1489.
[71]Garcia Frade LJ,de la Calle H,Alava I,et al.Diabetes mellitus as a hypercoagulable state:its relationship with fibrin fragments and vascular damage[J].Thromb Res,1987,47(5):533-540.
[72]Ford I,Singh TP,Kitchen S,et al. Activation of coagulation in diabetes mellitus in relation to the presence of vascular complications[J].Diabetes Med,1991,8(4):322-329.
[73]Carmassi F,Morale M,Puccetti R,et al.Coagulation and fibrinolytic system impairment in insulin dependent diabetes mellitus[J].Thromb Res,1992,67(6):643-654.
[74]Ceriello A,Quatraro A,Dellb Russo P,et al.Protein C deficiency in insulin-dependent diabetes:a hyperglycemia-related phenomenon[J].Thromb Haemost,1990,64(1):104-107.
[75]Cooper ME,Gilbert RE,Epstein M.Pathophysiology of diabetic nephropathy[J].Metabolism,1998,47(12 Suppl 1):3-6.
[76]The Diabetes Control and Complications Trail Research Group.The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus[J].N Engl J Med,1993,329(14):977-986.
[77]Tribe RM,Poston L.Oxidative stress and lipids in diabetes:a role in endothelium vasodilator dysfunction?[J] Vasc Med,1996,1(3):195-206.
[78]McMillan DE.Development of vascular complications in diabetesfJl. Vasc Med,1997,2(2):132-142.
[79]Baumgartner-Parzer SM,Wagner L,Pettermann M,et al.Modulation by high glucose of adhesion molecule expression in cultured endothelial cells[J].Diabetologia,1995,38(11):1367-1370.
[80]Brownlee M,Cerami A,Vlassara H.Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications[J].N Engl J Med,1988,318(20):1315-1321.
[81]Aronson D,Rayfield EJ.How hyperglycemia promotes atherosclerosis:molecular mechanisms[J].Cardiovasc Diabetol,2002,1:1.
[82]Vlassara H,Bucala R,Striker L.Pathogenic effects of advanced glycosylation:biochemical,biologic,and clinical implications for diabetes and aging[J].Lab Invest,1994,70(2):138-151.
[83]Brownlee M.Advanced protein glycosylation in diabetes and aging[J].Annu Rev Med,1995,46:223-234.
[84]Steinberg D.Low density lipoprotein oxidation and its pathobiological significance[J]. J Biol Chem,1997,272(34):20963-20966.
[85]Khoo JC,Miller E,McLoughlin P,et al.Enhanced macrophage uptake of low density lipoprotein after self-aggregation[J].Arteriosclerosis,1988,8(4):348-358.
[86]Ross R.Atherosclerosis-an inflammatory disease[J].N Engl J Med,1999,340(2):115-126.
[87]Griendling KK,Alexander RW.Oxidative stress and cardiovascular disease[J].Circulation,1997,96(10):3264-3265.
[88]Klein RL,Laimins M,Lopes-Virella MF.Isolation,characterization,and metabolism of the glycated and nonglycated subfractions of low-density lipoproteins isolated from type I diabetic patients and nondiabetic subjects[J].Diabetes,1995,44(9):1093-1098.
[89]Dzau VJ.Theodore Cooper Lecture:Tissue angiotensin and pathobiology of vascular disease,a unifying hypothesis[J].Hypertension,2001,37(4):1047-1052.
[90]Bucala R,Makita Z,Koschinsky T,et al.Lipid advanced glycosylation:pathway for lipid oxidation in vivo[J].Proc Natl Acad Sci USA,1993,90(14):6434-6438.
[91]Ferri C,Bellini C,Desideri G,et al.Plasma endothelin-1 level in obese hypertensive and normotensive man[J].Diabetes,1995,44(4):431-436.
[92]Hunter SJ,Garvey WT.Insulin action and insulin resistance:diseases involving defects in insulin receptors,signal transduction,and the glucose transport effector system[J].Am J Med,1998,105(4):331-345.
[93]Sowers JR,Sowers PS,Peuler JD.Role of insulin resistance and hyperinsulinemia in development of hypertension and atherosclerosis[J].J Lab Clin Med,1994,123(5):647-652.
[94]Reaven GM,Lithell H,Landsberg L.Hypertension and associated metabolic abnormalities-the role of insulin resistance and sympathoadrenal system[J].N Engl J Med,1996,334(6):374-381.
[95]McFarlane SI,Banerji M,Sowers JR.Insulin resistance and cardiovascular disease[J].J Clin Endocrinol Metab,2001,86(2):713-718.
[96]Meigs JB,D'Agostino RB Sr,Wilson PW,et al.Risk variable clustering in the insulin resistance syndrome.The Framingham offspring study[J].Diabetes,1997,46(10):1594-1600.
[97]Verma S,Wang CH,Li SH,et al.A self-fulfilling prophecy C-reactive protein attenuates nitric oxide production and inhibits angiogenesis[J].Circulation,2002,106(8):913-919.
[98]Gilbert RE,Rumble JR,Cao ZM,et al.Endothelin receptor antagonism ameliorates mast cell infiltration,vascular hypertrophy,and epidermal growth factor expression in experimental diabetes[J].Circ Res,2000,86(2):158-165.
[99]Bagdonaite L,Kucinskiene Z.Role of cytokines in cardiovascular disease[J].Seminars in Cardiology,2004,10(1):11-14.
[100]Tedgui A,Mallat Z.Anti-inflammatory mechanisms in the vascular wall[J].Circ Res,2001,88(9):877-887.
[101]Blake GJ,Ridker PM.Novel clinical markers of vascular wall inflammation[J].Cir Res,2001,89(9):763-771.
[102]Feener EP,King GL.Vascular dysfunction in diabetes mellitus[J].Lancet,1997,350(Suppl1):S19-S13.
[103]Koya D,King GL.Protein kinase C activation and the development of diabetic complications[J].Diabetes,1998,47(6):859-866.
[104]Park JY,Takahara N,Gabriele A,et al.Induction of endothelin-1 expression by glucose:an effect of protein kinase C activation[J].Diabetes,2000,49(7):1239-1248.
[105]Inaba T,Ishibashi S,Gotoda T,et al.Enhanced expression of platelet-derived growth factor-beta receptor by high glucose.Involvement of platelet-derived growth factor in diabetic angiopathy[J].Diabetes,1996,45(4):507-512.
[106]Blankenberg FQWen P,Zhu D,et al.Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabetic Zucker rats[J].Pediatr Radiol,2001,31(12):827-835.
[107]Tesfamariam B,Cohen RA.Free radicals mediate endothelial cell dysfunction caused by elevated glucose[J].Am J Physiol,1992,263 (2 pt 2):H321-H326.
[108]Giugliano D,Ceriello A,Paolisso G.Oxidative stress and diabetic vascular complications[J].Diabetes Care,1996,19(3):257-267.
[109]Vozarova B,Weyer C,Lindsay RS,et al.High white blood cell count is associated with a worsening of insulin sensitivity and predicts the development of type 2 diabetes[J].Diabetes,2002,51 (2):455-461.
[110]Hansen LK,Grimm RH Jr,Neaton JD.The relationship of white blood cell count to other cardiovascular risk factors [J].Int J Epidemiol,1990,19(4):881-888.
[111]Ernst E,Hammerschmidt DE,Bagge U,et al.Leukocytes and the risk of ischemic diseases[J].JAMA,1987,257(17):2318-2324.
[112]Glowacka E,Banasik M,Lewkowicz P,et al.The effect of LPS on neutrophils from the patients with high risks of type 1 diabetes mellitus in relation to IL-8、 IL-10 and IL-12 production and apoptosis in vitro[J].Scand J Immunol,2002,55(2):210-217.
[113]Fusman R,Rotstein R,Zeltser D,et al.The state of leukocyte adhesiveness/aggregation in the peripheral blood of patients with type 2 diabetes and ischemic vascular disease[J].Acta Diabetol,2001,38(1):43-49.
[114]Schieffer B,Schieffer E,Hilfiker-Kleiner D,et al.Expression of angiotensin Ⅱ and interleukin 6 in human coronary atherosclerotic plaques:potential implications for inflammation and plaque instability[J].Circulation,2000,101(12):1372-1378.
[115]Diet F,Pratt RE,Berry GJ,et al.Increased accumulation of tissue ACE in human atherosclerotic coronary artery disease[J].Circulation,1996,94(11):2756-2767.
[116]UK Prospective Diabetes Study(UKPDS)Group.Intensive blood-glucose control with sulphonylureas of insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes(UKPDS 33)[J].Lancet,1998;352:837-853.
[117]Brenner BM,Cooper ME,de Zeeuw D,et al,for the RENAAL Study Investigators.Effects of losartan on remal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy[J].N Engl J Med,2001,345(12):861-869.
[118]Lewis EJ,Hunsicker LG,Clarke WR,et al.for the Collaborative Study Group.Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes[J].N Engl J Med,2001,345(12):851-860.
[119]Parving HH,Lehnert H,Brochner-Mortensen J,et al.for the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group.The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes[J].N Engl J Med,2001,345(12):870-878.
[120]Heart Outcomes Prevention Evaluation Study Investigators.Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus:Results of the HOPE study and MICRO-HOPE substudy[J].Lancet,2000;355(9200):253-259.
[121]Jandeleit-Dahm KA,Tikellis C,Reid CM,et al. Why blockade of the rennin-angiotensin system reduces the incidence of new-onset diabetes[J].J Hypertens,2005,23(3):463-473.
[122]Dagenais GR,Yusuf S,Bourassa MG,et al.Effect of ramipril on coronary event in high-risk persons:result of the Heart Outcomes Prevention Evaluation study[J].Circulation,2001,104(5):522-526.
[123]方厚华,仇志华.糖尿病动物模型的研究进展[J].实验动物科学与管理,2004,18(2)：39-42.
[124]王宁,谢自敬,阿布力克木·吐尔地,等.糖尿病大鼠动脉粥样硬化与游离脂肪酸表达的关系[J].中国动脉硬化杂志,2005,13(5)：563-566.
[125]徐梓辉,周世文,钱桂生,等.2型糖尿病合并动脉粥样硬化大鼠模型的建立[J].中国病理生理杂志,2006,22(1)：205-208.
[126]陈丽萌,李学旺,黄利伟,等.2型糖尿病小鼠(KKAγ)动物模型的鉴定和早期肾脏病理改变[J].中国医学科学院学报,2002,24(1)：71-77.
[127]Cheng ZJ, Vaskonen T, Tikkanen I,et al. Endothelial dysfunction and salt-sensitive hypertension in spontaneously diabetic Goto-Kakizaki rats[J]. Hypertension,2001,37(2 Part 2):433-439.
[128]Ling ZC,Hong-Lie C,Ostenson CQet al.Hyperglycemia contributes to impaired insulin response in GK rat islets[J].Diabetes,2001;50(Suppl 1):S108-S112.
[129]Hughes SJ, Suzuki K, Goto Y. The role of islet secretory function in the development of diabetes in the GK Wistar rat[J]. Diabetologia,1994,37 (9):863-870.
[130]王宝金,代解杰.糖尿病动物模型的研究进展[J].上海实验动物科学,2003,23(2)：116-123.
[131]Zhao Q,Egashira K,Inoue S,et al.Vascular endothelial growth factor is necessary in the development of arteriosclerosis by recruiting/activating monocytes in a rat model of long-term inhibition of nitric oxide synthesis[J].Circulation,2002,105(9):1110-1115.
[132]Kataoka C,Egashira K,Ishibashi M,et al.Novel anti-inflammatory actions of amlodipine in a rat model of arteriosclerosis induced by long-term inhibition of nitric oxide synthesis[J].Am J Physiol Heart Circ Physiol,2004,286(2):H768-H774.
[133]Kataoka C,Egashira K,Inoue S,et al.Important role of Rho-kinase in the pathogenesis of cardiovascular inflammation and remodeling induced by long-term blockade of nitric oxide synthesis in rats[J].Hypertension,2002,39(2):245-250.
[134]Perrault LP,Malo O,Bidouard JP,et al.Inhibiting the NO pathway with intracoronary L-NAME infusion increases endothelial dysfunction and intimal hyperplasia after heart transplantation[J].J Heart Lung Transplant,2003,22(4):439-451.
[135]王芬,何华亮,张红敏,等.参芪复方对GK大鼠脂代谢异常的实验研究[J].天津中医药,2007,24(6)：507-508.
[136]谢毅强,李军茹,张红敏等.参芪复方治疗2型糖尿病胰岛素抵抗的临床研究[J].中华实用中西医杂志,2005,18(17)：844-846.
[137]张红敏,陈世伟,谢春光等.参芪复方对GK大鼠白色脂肪组织脂联素基因表达的影响[J].中成药,2006,28(7)：996-1001.
[138]张红敏,陈世伟,谢春光等.参芪复方抗自发性糖尿病GK大鼠早期动脉粥样硬化的作用机制[J].中国中药杂志,2006,31(15)：1272-1276.
[139]沈应君主编.中药药理学[M].人民卫生出版社,2000：96-97.
[140]Van de Ree MA, Huisman MV, Princen HM. Strong decrease of high sensitively C-reactive protein with high-dose atorvastatin in patients with type 2 diabetes mellitus[J]. Atherosclerosis,2003,166(1):129-135.
[141]Topol EJ. Intensive statin therapy-a sea change in cardiovascular prevention. N Engl J Med,2004,350(15):1562-1564.
[142]Auer J, Berent R, Weber T, et al. Clinical significance of pleiotropic effects of statins:lipid reduction and beyond[J].Curr Med Chem,2002,9(20):1831-1850.
[143]Lind L.Circulating markers of inflammation and atherosclerosis [J].Atherosclerosis,2003,169(2):203-214.
[144]Yuan M,Konstantopoulos N,Lee J,et al.Reversal of obesity-and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta[J].Science,2001,293(5535):1673-1677.
[145]Greenberg AS. The expanding scope of the metabolic syndrome and implications for the management of cardiovascular risk in type 2 diabetes with particular focus on the emerging role of the thiazolidinediones [J].J Diabetes Complications,2003,17(4):218-228.
[146]Dandona P, Aljada A,Mohanty P,et al.Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subiects:evidence for an anti-inflammatory effect[J]?J Clin Endocrinol Metab,2001,86(7):3257-3265.
[147]杨宝峰,苏定冯,周宏灏.《药理学》[M].第七版.北京.人民卫生出版社,2008：264-267.
[148]Cannon CP,Braunwald E,McCabe CH,et al.Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 investigatiors.Intensive versus moderate lipid lowering with statins after acute coronary syndromes(PROVE-IT Study) [J].N Engl J Med,2004,350(15):1495-1504.
[149]Stepp DW,Ou J,Ackerman AW,et al.Native LDL and minimally oxidized LDL differentially regulate superoxide anion in vascular endothelium in situ[J].Am J Physiol Heart Circ Physiol,2002,283(2):H750-759.
[150]Ou J,Ou Z,Jones DW,et al.L-4F,an apolipoprotein A-1 mimetic,dramatically improves vasodilation in hypercholesterolemia and sickle cell disease [J].Circulation,2003,107(18):2337-2341.
[151]Mason RP,Walter MF,Jacob RF.Effects of HMG-CoA reductase inhibitors on endothelial function:role of microdomains and oxidative stress [J].Circulation,2004,109(Suppl1):Ⅱ34-41.
[152]Bruemmer D,Yin F,Liu j,et al.Atorvastatin inhibits expression of minichromosome maintenance proteins in vascular smooth muscle cells[J].Eur Pharmacol,2003,462(1-3):15-23.
[153]Libby P,Aikawa M.Mechanisms of plaque stabilization with statins[J].Am J Cardiol,2003,91 (4A),4B-8B.
[154]Bea F,Blessing E,Bennett B,et al.Simvastatin promotes atherosclerotic plaque stability in apoE-deficient mice independently of lipid lowering[J].Arterioscler Thromb Vasc Biol,2002,22(11):1832-1837.
[155]Backes JM,Howard PA,Moriarty PM.Role of C-reactive protein in cardiovascular disease[J].Ann Pharmacother,2004,38(1):110-118.
[156]Horne BD,Muhlestein JB,Carlquist JF,et al.Intermoutain Heart Collaborative(IHC) Study Group:Statin therapy interacts with cytomegalovirus seropositivity and high C-reactive protein in reducing mortality among patients with angiographically significant coronary disease[J].Circulation,2003,107(2):258-263.
[157]Bonetti PO,Lerman LO,Napoli C,et al.Statin effects beyond lipid lowering-are they clinically relevant[J]?Eur Heart J,2003,24(3):225-248.
[158]Rezaie-Majd A,Prager GW,Bucek RA,et al.Simvastatin reduces the expression of adhesion molecules in circulating monocytes from hypercholesterolemic patients [J].Arterioscler Thromb Vasc Biol,2003,23(3):397-403.
[159]Weitz-Schmidt G,Welzenbach K,Brinkmann V,et al.Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site[J].Nat Med,2001,7(6):687-692.
[160]Sposito AC,Chapman MJ.Statin therapy in acute coronary syndromes:mechanistic insight into clinical benefit[J].Arterioscler Thromb Vasc Biol,2002,22(10):1524-1534.
[161]Saijonmaa O,Nyman T,Fyhrguist F.Atorvastatin inhibits angiotensin-converting enzyme induction in differentiating human marophages[J].Am J Physiol Heart Circ Physiol,2007,292(4):H1917-1921.
[162]Ito T,Ikeda U,Yamamoto K,et al.Regulation of interleukin-8 expression by HMG-CoA reductase inhibitors in human vascular smooth muscle cells[J].Atherosclerosis,2002,165(1):51-55.
[163]Landsberger M, Wolff B,Jantzen F,et al.Cerivastatin reduces cytokine-induced surface expression of ICAM-1 via increased shedding in human endothelial cells[J].Atherosclerosis,2007,190(1):43-52.
[164]Nickenig G,Baumer AT,Temur Y,et al.Statin-sensitive dysregulated AT1 receptor function and density in hypercholesterolemic men [J].Circulation,1999,100(21):2131-2134.
[165]Seljeflot I,Tonstad S,Hjermann I,et al.Reduced expression of endothelial cell markers after 1 year treatment with simvastatin and atorvastatin in patients with coronary heart disease[J].Atherosclerosis,2002,162(1):179-185.
[166]Heart Protection Study Collaborative Group.MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals:a randomised placebo-controlled trial[J].Lancet,2002,360(9326):7-22.
[167]Colhoun HM,Betteridge DJ,Durrington PN,et al.Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study(CARDS):Multicentre randomised placebo-controlled trial.Lancet,2004,364(9435):685-696.
[168]黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算[J].中国临床药理学与治疗学,2004,9(9)：1069-1072.
[169]李稻主编.医学功能学科—实验原理与方法[M].人民卫生出版社,北京：2008,33-35.
[170]Barzilay JI,Abraham L,Heckbert SR,et al.The relation of markers of inflammation to the development of glucose disorders in the elderly:the Cardiovascular Health Study[J].Diabetes,2001,50(10):2384-2389.
[171]Festa A,DAgostino RJ,Howard Qet al.Chronic subclinical inflammation as part of the insulin resistance syndrome:the Insulin Resistance Atherosclerosis Study(IRAS)[J].Circulation,2000,102(1):42-47.
[172]Visser M,Bouter LM,Mc Quillan GM,et al.Elevated C-reactive protein levels in overweight and obese adults[J].JAMA,1999,282(22):2131-2135.
[173]Ridker PM,Cushman M,Stampfer MJ,et al.Inflammation,aspirin and risk of cardiovascular disease in apparently health men[J].N Engl J Med,1997,336(14):973-979.
[174]Fiordaliso F,Leri A,Cesselli D,et al.Hyperglycemia activates p53 and p53-regulated genes leading to myocyte cell death[J].Diabetes,2001;50(10):2363-2375.
[175]Leri A,Claudio PP,Li Q,et al.Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell[J].J Clin Invest,1998,101(7):1326-1342.
[176]Leri A,Liu Y,Wang X,et al.Overexpression of insulin-like growth factor-1 attenuates the myocyte renin-angiogensin system in transgenic mice[J].Circ Res,1999,84(7):752-762.
[177]Leri A,Fiordaliso F,Setoguchi M,et al.Inhibition of p53 function prevents renin-angiotensin system activation and stretch-mediated myocyte apoptosis[J].Am J Pathol,2000,157(3):843-857.
[178]He W,Miao FJ,Lin DC,et al.Critic acid cycle intermediates as ligands for orphan G-protein-coupled receptors[J].Nature,2004,429(6988):188-193.
[179]Toma I,Kang JJ,Sipos A,et al.Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney[J].J Clin Invest,2008,118(7):2526-2534.
[180]Rajagopalan S,Harrison DGReversing endothelial dysfunction with ACE inhibitors:A new TREND[J].Circulation,1996,94(3):240-243.
[181]曾朝荣,兰永乔.动脉内皮与心血管疾病[J].中国心血管病杂志,2001,6(1)：47-50.
[182]Rajagopalan S,Kurz S,Munzel T,et al.Angiotensin Ⅱ-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation:Contribution to alternation of vasomotor tone[J].J Clin Invest,1996,97(8):1916-1923.
[183]Harrison DG,Cai H.Endothelial control of vasomotion and nitric oxide production.Cardiol Clin,2003,21(3):289-302.
[184]景涛,何国祥,刘建平,等.血管紧张素Ⅱ对血管平滑肌细胞粘着斑及肌动蛋白细胞骨架组装的影响及意义[J].第三军医大学学报.2001,10(23)：1173-1176.
[185]Rubin P,Williams J P,Riggs P N,et al.Cellular and molecular mechanisms of radiation inhibition of restenosis.Part Ⅰ:role of the macrophage and platelet-derived growth factor[J].Int J Radiat Oncol Biol Phys,1998,40(4):929-941.
[186]Sironi L,Calvio AM,Arnaboldi L,et al.Effect of valsartan on angiotensin II-induced plasminogen activator inhibitor-1 biosynthesis in arterial smooth muscle cells[J].Hypertension,2001,37(3):961-966.
[187]Labinjoh C,Newby DE,Dawson P,et al.Fibrinolytic actions of intra-arterial angiotensin II and bradykinin in vivo in man[J].Cardiovasc Res,2000,47(4):707-714.
[188]Lusis AJ,Atherosclerosis[J].Nature,2000,407(6801):233-241.
[189]Morawietz H,Rueckschloss U.Angiotensin Ⅱ induces LOX-1,the human endothelial receptor for oxidized low-density lipoprotein[J].Circulation,1999,100(9):899-902.
[190]Touyz RM.Molecular and cellular mechanisms in vascular injury in hypertension:role of angiotensin Ⅱ [J].Curr Opin Nephrol Hypertens,2005,14(2):125-131.
[191]Kranzhfer R,Browatzki M,Schmidt J,et al.Angiotensin Ⅱ activates the proinflammatory transcription factor nuclear factor-kappaB in human monocytes[J].Biochem Biophys Res Commun,1999,257(3):826-828.
[192]Pueyo ME,Gonzalez W,Nicoletti A,et al.Angiotensin Ⅱ stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor-kappaB activation induced by intracellular oxidative stress[J].Arterioscler Thromb Vasc Biol,2000,20(3):645-51.
[193]Tham DM,Maetin-Mcnulty B,Wang YX,et al.Angiotensin Ⅱ is associated with activation of NF-к B-mediated genes and downregulation of PPARs[J].Physiol Genomics,2002,11(1):21-36.
[194]Kato H,Suzuki H,Tajima S,et al.Angiotensin Ⅱ stimulates collagen synthesis in cultured vascular smooth muscle cells[J].J Hypertens,1991,9(1):17-22.
[195]Mifune M,Sasamura H,Shimizu-Hirota R,et al.Angiotensin II type 2 receptors stimulate collagen synthesis in cultured vascular smooth muscle cells[J].Hypertension,2000,36(5):845-850.
[196]Ju H,Dixon IM.Extracellular matrix arid cardiovascular diseases[J].Can J Cardiol,1996,12(12):1259-1267.
[197]Iozzo RV.Matrix proteoglycans:from molecular design to cellular function[J].Annu Rev Biochem,1998,67:609-652.
[198]Sasamura H,Shimizu-Hirota R,Nakaya H,Saruta T.Effect of ATI receptor antagonist on proteoglycan gene expression in hypertensive rats[J].Hypertens Res,2001,24(2):165-172.
[199]Moriguchi Y,Matsubara H,Mori Y,et al.Angiotensin Ⅱ-induced transactivation of epidermal growth factor receptor regulates fibronectin and transforming growth factor-beta synthesis via transcriptional and posttranscriptional mechanisms[J].Circ Res,1999,84(9):1073-1084.
[200]Libby P,Lee RT.Matrix matters[J].Circulation,2000,102(16):1874-1876.
[201]Chen X,Li W,Yoshida H,et al.Targeting deletion of angiotensin type 1B receptor gene in the mouse[J].Am J Physiol,1997,272(3 pt 2):F299-F304.
[202]Bonnardeaux A,Davies E,Jeunemaitre X,et al.Angiotensin Ⅱ type 1 receptor gene polymorphisms in human essential hypertension[J].Hypertension,1994,24(1):63-69.
[203]Benetos A,Topouchian J,Ricard S,et al.Influence of angiotensin Ⅱ type 1 receptor polymorphism on aortic stiffness in never-treated hypertensive patients[J].Hypertension,1995;26(1):44-47.
[204]Berge KE,Bakken A,Bohn M,et al.A DNA polymorphism at the angiotensin Ⅱ type 1 receptor(AT1R) locus and myocardial infarction[J].Clin Genet,1997,52(2):71-76.
[205]AbdAlla S,Lother H,Abdel-tawab AM,et al.The angiotensin Ⅱ. AT2 receptor is an AT1 receptor antagonist[J].J Biol Chem,2001,276(43):39721-39726.
[206]Hansen JL,Theilade J,Haunso S,et al.Oligomerization of wild type and nonfunctional mutant angiotensin Ⅱ type Ⅰ receptors inhibits galphaq protein signaling but not ERK activation[J].J Biol Chem,2004,279(23):24108-24115.
[207]Barki-Harrington L,Luttrell LM,Rockman HA.Dual inhibition of beta-adrenergic and angiotensin Ⅱ receptors by a single antagonist:a functional role for receptor-receptor interaction in vivo[J].Circulation,2003,108(13):1611-1618.
[208]Touyz RM,He G,Deng LY,et al.Role of extracellular signal-regulated kinases in angiotensin Ⅱ-stimulated contraction of smooth muscle cells from human resistance arteries[J].Circulation,1999,99(3):392-399.
[209]Mehta PK,Griendling KK.Angiotensin Ⅱ cell signaling:physiological and pathological effects in the cardiovascular system[J].Am J Physiol Cell Physiol,2007,292(1):C82-C97.
[210]Nickenig G,Jung O,Strehlow K,et al.Hypercholesterolemia is associated with enhanced angiotensin AT1-receptor expression[J].Am J Physiol,1997,272(6 pt 2):H2701-2707.
[211]Nickenig G,Sachinidis A,Michaelsen F,et al.Upregulation of vascular angiotensin Ⅱ receptor gene expression by low-density lipoprotein in vascular smooth muscle cells[J].Circulation,1997,95(2):473-478.
[212]Griendling KK,Lassegue B,Alexander RW.Angiotensin recepors and their therapeutic implications[J]. Annu Rev Pharmacol Toxicol,1996,36:281-306.
[213]Mukoyama M,Nakajima M,Horiuchi M,et al.Expression cloning of type 2 angitensin Ⅱ receptor reveals a unique class of seven-transmembrane receptors[J].J Biol Chem,1993,268(33):24539-24542.
[214]Shanmugam S,Corvol P,Gasc JM.Angiotensin Ⅱ type 2 receptor mRNA expression in the developing cardiopulmonary system of the rat[J].Hypertension,1996,28(1):91-97.
[215]Tsutsumi Y,Matsubara H,Ohkubo N,et al. Angiotensin Ⅱ type 2 receptor is upregulated in human heart with interstitial fibrosis,and cardiac fibroblasts are the major cell type type for its expression[J].Circ Res,1998,83(10):1035-1046.
[216]Bedecs K,Elbaz N,Sutren M,et al.Angiotensin Ⅱ type 2 receptors mediate inhibition of mitogen-activated protein kinase cascade and functional activation of SHP-1 tyrosine phosphatase[J].Biochem J,1997,325(pt 2):449-454.
[217]Munzenmaier DH,Greene AS.Opposing action of angiotensin Ⅱ on microvascular growth and arterial blood pressure[J].Hypertension,1996,27(3 pt 2):760-765.
[218]Bumpus FM,Catt KJ,Chiu AT,et al.Nomenclature for angiotensin receptors. A report of the Nomenclature Committee of the Council for High Blood Pressure Research[J].Hypertension,1991,17(5):720-721.
[219]Jobin C,Hellerbrand C,Licato LL,et al.Mediation by NF-kappa B of cytokine induced expression of intercellular adhesion molecule 1(ICAM-1) in a intestinal epithelial cell line,a process blocked by proteasome inhibitors[J].Gut,1998,42(6):779-787.
[220]Roebuck KA,Finnegan A.Regulation of intercellular adhesion molecule-1 (CD54) gene expression[J].J Leukoc Biol,1999,66(6):876-888.
[221]Wissink S,van de Stolpe A,Caldenhoven E,et al.NF-kappa B/Rel family members regulating the ICAM-1 promoter in monocytic THP-1 cells[J].Immunobiology,1997,198(1-3):50-64.
[222]Osborn L,Hession C,Tizard R,et al.Direct expression cloning of vascular cell adhesion molecule 1,a cytokine-induced endothelial protein that binds to lymphocytes[J].Cell,1989,59(6):1203-1211.
[223]Paine R 3rd,Ward PA.Cell adhesion molecules and pulmonary fibrosis[J].Am J Med,1999,107(3):268-279.
[224]Macphee CH,Nelson JJ,Zalewski A.Lipoprotein-associated phosphlipase A2 as a target of therapy[J].Curr Opin Lipidol,2005,16(4):442-446.
[225]Karabina SA,Brocheriou I,Le Naouy Qet al.Atherogenic properties of LDL particles modified by human group X secreted phospholipase A2 on human endothelial cell function[J].FASEB J,2006,20(14):2547-2549.
[226]O'Brien KD,McDonald TO,Chait A,et al.Neovascular expression of E-selectin,intercellular adhesion molecule-1,and vascular cell adhesion molecule-1 in human atherosclerosis and their relation to intimal leukocyte content[J].Circulation,1996,93(4):672-682.
[227]Cybulsky MI,Iiyama K,Li H,et al.A major role for VCAM-l,but not ICAM-1,in early atherosclerosis[J].J Clin Invest,2001,107(10):1255-1262.
[228]Costanzo A,Moretti F,Burgio V,et al.Endothelial activation by angiotensin Ⅱ through NFkappaB and p38 pathways:Involvment of NFkappaB-inducible kinase (NIK),free oxygen radicals,and selective inhibition by aspirin[J].J Cell Physiol,2003,195(3):420-410.
[229]张红敏,陈世伟,谢春光,等.参芪复方对GK大鼠炎症标志物的影响及机理探讨[J].中药材,2006,29(3)：249-253.
1 Ruschitzka FT,Noll QLuscher TF.The endothelium in coronary artery disease[J].Cardiology,1997,88 Suppl 3:3-19.
2 Rajagopalan S,Harrison D G.Reversing endothelial dysfunction with ACE inhibitors:A new trend[J].Circulation,1996,94(3):240-243.
3曾朝荣,兰永乔.动脉内皮与心血管疾病[J].中国心血管病杂志,2001,6(1)：47-50.
4 Rajagopalan S,Kurz S,Munzel T,et al.Angiotensin Ⅱ-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation:Contribution to alternation of vasomotor tone[J].J Clin Invest,1996,97(8):1916-1923.
5 Harrison DG,Cai H.Endothelial control of vasomotion and nitric oxide production[J].Cardiol Clin,2003,21(3):289-302.
6 Kuroski de Bold ML.Estrogen,natriuretic peptides and the renin-angiotensin system[J].Cardiovasc Res,1999,41 (3):524-531.
7 Itoh H,Mukoyama M,Pratt RE,et al.Multiple autocrine growth fators modulate vascular smooth muscle cells growth response to angiotensin-Ⅱ [J].J Clin Invest,1993,91 (5):2268-2274.
8郭涛,任大宏.ANG-Ⅱ、ANP对培养的人血管内皮细胞bFGF表达的影响[J].中国组织化学与细胞化学杂志,2002,11(3)：319-322.
9任大宏,曾晓坤.自发性高血压大鼠高血压进展期肠系膜动脉的超微结构变化[J].同济医科大学学报.1998,27(6)：417-419.
10 Mulvany MJ, Vascular remodelling of resistance vessels:can we define this[J]?Cardiovasc Res,1999,41 (1):9-13.
11 Rubin P,Williams J P,Riggs P N,et al.Cellular and molecular mechanisms of radiation inhibition of restenosis.Part Ⅰ:role of the macrophage and platelet-derived growth factor[J].Int J Radiat Oncol Biol Phys,1998,40(4):929-941.
12 Cary LA,Guan J L.Focal adhesion kinase in integrin-mediated signaling[J].Front Biosci,1999,4(3):D102-113.
13 Castellano F,Montcourrier P,Guillenmot J C,et al.Inducible recruitment of Cdc42 or WASP to a cell-surface receptor triggers actin polymerization and filopodium formation [J].Curr Biol,1999,9(7):351-360.
14景涛,何国祥,刘建平,等.血管紧张素Ⅱ对血管平滑肌细胞粘着斑及肌动蛋白细胞骨架组装的影响及意义[J].第三军医大学学报.2001,10(23)：1173-1176.
15 Folsom AR.Fibrinolytic factors and atherothrombotic events:epidemiological evidence[J]. Ann Med,2000,32 suppl 1:85-91.
16 Sironi L,Calvio AM,Arnaboldi L,et al.Effect of valsartan on angiotensin Ⅱ-induced plasminogen activator inhibitor-1 biosynthesis in arterial smooth muscle cells[J].Hypertension,2001,37(3):961-966.
17 Labinjoh C,Newby DE,Dawson P,et al.Fibrinolytic actions of intra-arterial angiotensin Ⅱ and bradykinin in vivo in man.Cardiovasc Res,2000,47(4):707-714.
18 Lusis AJ, Atherosclerosis[J].Nature,2000,407(6801):233-241.
19 Morawietz H,Rueckschloss U. Angiotensin Ⅱ induces LOX-1,the human endothelial receptor for oxidized low-density lipoprotein[J].Circulation,1999,100(9):899-902.
20 Uehara Y,Urata H,Sasaguri M,et al.Increased chymase activity in internal thoracic artery of patients with hypercholesterolemia[J].Hypertension,2000,35 (1 Pt 1):55-60.
21 Suzuki Y,Ruiz-Ortega M,Lorenzo O,et al.Inflammation and angiotensin Ⅱ[J]. Int J Biochem Cell Biol,2003,35(6):881-900.
22车在前,等.血管紧张素Ⅱ诱导血管外膜成纤维细胞产生结缔组织生长因子.高血压杂志,2005,5(13)：301-305.
23 Touyz RM.Molecular and cellular mechanisms in vascular injury in hypertension:role of angiotensin Ⅱ.Curr Opin Nephrol Hypertens,2005,14(2):125-131.
24 Kranzhfer R,Browatzki M,Schmidt J,et al.Angiotensin Ⅱ activates the proinflammatory transcription factor nuclear factor-kappaB in human monocytes[J].Biochem Biophys Res Commun,1999,257(3):826-828.
25 Pueyo ME,Gonzalez W,Nicoletti A,et al.Angiotensin Ⅱ stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor-kappaB activation induced by intracellular oxidative stress[J].Arterioscler Thromb Vasc Biol,2000,20(3):645-51.
26 Tham DM,Maetin-Mcnulty B,Wang YX,et al.Angiotensin Ⅱ is associated with activation of NF-к B-mediated genes and downregulation of PPARs[J].Physiol Genomics,2002,11(1):21-30.
27 Arenas IA,Xu Y,Lopez-Jaramillo P,et al.Angiotensin Ⅱ-induced MMP-2 release from endothelial cells is mediated by TNF-alpha[J].Am J Physiol cell Physiol,2004,286(4):C779-C784.
28 Kalra D,Sivasubramanian N,Mann DL.Angiotensin Ⅱ induces tumor necrosis factor biosynthesis in the adult mammalian heart through a protein kinase-dependent pathway[J].Circulation,2002,105(18):2198-2205.
29 Kato H,Suzuki H,Tajima S,et al.Angiotensin Ⅱ stimulates collagen synthesis in cultured vascular smooth muscle cells[J].J Hypertens,1991,9(1):17-22.
30 Mifune M,Sasamura H,Shimizu-Hirota R,et al.Angiotensin Ⅱ type 2 receptors stimulate collagen synthesis in cultured vascular smooth muscle cells[J].Hypertension,2000,36(5):845-850.
31 Ju H,Dixon IM.Extracellular matrix and cardiovascular diseases[J].Can J Cardiol,1996,12(12):1259-1267.
32 Iozzo RV.Matrix proteoglycans:from molecular design to cellular function[J].Annu Rev Biochem,1998,67:609-652.
33 Sasamura H,Shimizu-Hirota R,Nakaya H,Saruta T.Effect of AT1 receptor antagonist on proteoglycan gene expression in hypertensive rats[J].Hypertens Res,2001,24(2):165-172.
34 Moriguchi Y,Matsubara H,Mori Y,et al.Angiotensin Ⅱ-induced transactivation of epidermal growth factor receptor regulates fibronectin and transforming growth factor-beta synthesis via transcriptional and posttranscriptional mechanisms[J].Circ Res,1999,84(9):1073-1084.
35 Libby P,Lee RT.Matrix matters[J].Circulation,2000,102(16):1874-1876.
[2]卫生部疾病控制司,中华医学会糖尿病学分会.《中国糖尿病防治指南》试行本节选[J].中国慢性病预防与控制,2004,12(6)：283-285.
[3]Kanaya AM,Grady D,Barrett-Connor E.Explaining the sex difference in coronary heart disease mortality among patients with type 2 diabetes mellitus:a meta-analysis[J].Arch Intern Med,2002,162(15):1737-45.
[4]American Diabetes Association.Economic consequences of diabetes mellitus in the U.S. in 1997[J].Diabetes Care,1998,21(2):296-309.
[5]Fiordaliso F,Li B,Latini R,et al.Myocyte death in streptozotocin-induced diabetes in rats in angiotensin Ⅱ-dependent[J].Lab Invest,2000,80(4):513-517.
[6]Kajstura J,Fiordaliso F,Andreoli AM,et al.IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and angiotensin Ⅱ-mediated oxidative stress[J].Diabetes,2001,50(6):1414-1424.
[7]全国糖尿病研究协作组调查研究组.全国14省市30万人口中糖尿病调查报告[J].中华内科杂志,1981,20(11)：678-83.
[8]Pan XR,Yang WY,Liu J.Prevalence of diabetes and its risk factors in China,1994[J].National Diabetes Prevention and Control Cooperative Group.Diabetes Care,1997,20(11):1664-9.
[9]http://www.eatlas.idf.org/Prevalence/.
[10]中华医学会糖尿病学分会慢性并发症调查组.1991-2000年全国住院糖尿病患者慢性并发症及相关大血管病变回顾性分析[J].中国医学科学院学报,2002,24(5)：447-51.
[11]田代华整理.黄帝内经素问[M].北京：人民卫生出版社,2005：59.
[12]田代华整理.黄帝内经素问[M].北京：人民卫生出版社,2005：116.
[13]汉·张仲景著,何任,何若苹整理.金匮要略[M].北京：人民卫生出版社,2005：50.
[14]明·戴原礼撰,王英,江凌圳,竹剑平整理.秘传证治要诀及类方[M].北京：人民卫生出版社,2006：85.
[15]明·张介宾撰,李继明王大涥等整理.景岳全书[M].北京：人民卫生出版社,2005：422.
[16]田代华整理.黄帝内经素问[M].北京：人民卫生出版社,2005：93.
[17]田代华,刘更生整理.灵枢经[M].北京：人民卫生出版社,2005：97-98.
[18]宋·赵佶编.圣济总录[M].北京：人民卫生出版社,1982：1064-1099.
[19]许敬生主编.罗天益医学全书[M].北京：中国中医药出版社,2006：101.
[20]田代华整理.黄帝内经素问[M].北京：人民卫生出版社,2005：15.
[21]田代华,刘更生整理.灵枢经[M].北京：人民卫生出版社,2005：95.
[22]清·叶天士撰,苏礼,焦振廉等整理.临证指南医案[M].北京：人民卫生出版社,2005：271.
[23]唐·王焘撰,外台秘要[M].北京：人民卫生出版社,1982：306.
[24]汉·张仲景著,何任,何若苹整理.金匮要略[M].北京：人民卫生出版社,2005：51.
[25]宋·王怀隐等编.太平圣惠方[M].北京：人民卫生出版社,1982：1624.
[26]宋乃光主编.刘完素医学全书[M].北京：中国中医药出版社,2006：274.
[27]明·李梃原著,田代华,金丽,何永点校.医学入门[M].天津：天津科学技术出版社,2000：880.
[28]明·张介宾撰,李继明王大涥等整理.景岳全书[M].北京：人民卫生出版社,2005：423-424.
[29]清·叶天士撰,苏礼,焦振廉等整理.临证指南医案[M].北京：人民卫生出版社,2005：272.
[30]中国中西医结合学会糖尿病专业委员会.中西医结合糖尿病诊疗标准(草案)[J].中国中西医结合杂志,2005,25(1)：94-95.
[31]林兰.现代中医糖尿病学[M].北京：人民卫生出版社,2008：737.
[32]梁平茂,曹克光.2型糖尿病血管并发症中医病机探讨[J].中医杂志,2006,47(10)：726.
[33]李振中,尹翠梅.痰浊瘀血与糖尿病血管病变理论探讨[J].中西医结合心脑血管病杂志,2005,3(11)：983-985.
[34]李步满,吴深涛,吴丽丽.2型糖尿病血管并发症与“阴火”病机的相关性探讨[J].辽宁中医杂志,2007,34(9)：1229-1231.
[35]王苢生,赵文景,夏军,等.益气养阴活血方对气阴两虚血瘀型糖尿病患者血浆内皮素与一氧化氮水平的影响[J].中国中西医结合杂志,2000,20(8)：571-573.
[36]Creager MA,Luscher TF, Cosentino F,et al.Diabetes and vascular disease:pathophysiology,clinical consequences and medical therapy:part I [J].Circulation,2003:108[12]:1655-1661.
[37]Luscher TF,Creager MA,Beckman JA,et al.Diabetes and vascular disease:pathophysiology,clinical consequences and medical therapy:part II [J].Circulation,2003:108(13):1527-1532.
[38]Beckman JA.Pathophysiology of vascular dysfunction in diabetes[J].Cardiology Rounds,2004,8(10):1-5.
'[39]Kadirvelu A,Han CK,Lang CC.Endothelial dysfunction in cardiovascular diseases[J].Med Prog,2002,May:4-10.
[40]Drexler H,Hornig B.Endothelial dysfunction in human disease[J].J Mol Cell Cardiol,1999;31(1):51-60.
[41]van der Loo B,Labugger R,Skepper JN,et al.Enhanced peroxynitrite formation is associated with vascular aging[J].J Exp Med,2000,192:1731-1744.
[42]Taylor PD,Poston L.The effect of hyperglycaemia on function of rat isolated mesenteric resistance artery[J].Br J Pharmacol,1994; 113:801-808.
[43]Tooke JE.Microvascular function in human diabetes. A physiological perspective[J].Diabetes,1995;44(7):721-726.
[44]Rattan V,Sultana C,Shen Y,et al.Oxidant stress-induced transendothelial migration of monocytes is linked to phosphorylation of PEC AM-1[J]. Am J Physiol,1997;273(3 pt 1):E453-E461.
[45]Tesfamariam B,Brown ML,Cohen RA.Elevated glucose impaires endothelium-dependent relaxation by activating protein kinase C[J].J Clin Invest,1991;87(5):1643-1648.
[46]Poston L,Taylor PD.Glaxo/MRS Young Investigator Prize.Endothelium-mediated vascular function in insulin-dependent diabetes mellitus[J].Clin Sci(Lond),1995,88(3):245-255.
[47]Furchgott RF,Zawadzki JV.The obligatory role of the endothelial cells in the relaxation of arterial smooth muscle by acetylcholine[J].Nature,1980,288(5789):373-376.
[48]Cines DB,Pollak ES,Buck CA,et al.Endothelial cells in physiology and in the pathophysiology of vascular disorders[J].Blood,1998,91(10):3527-3561.
[49]Storey AM,Perry CJ,Petrie JR.Endothelial dysfunction in Type 2 diabetes[J].Br J Diabetes Vasc Dis,2001,1(1):22-27.
[50]Baynes JW.Role of oxidative stress in development of complication in diabetes[J].Diabetes,1991,40(4):405-412.
[51]Morigi M,Angioletti S,Imberti B,et al.Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-K B-dependent fashion[J].J Clin Invest,1998,101(9):1905-1915.
[52]Cagliero E,Roth T,Roy S,et al.Characteristics and mechanisms of high-glucose-induced overexpresssion of basement membrane components in cultured human endothelial cells[J].Diabetes,1991,40(1):102-110.
[53]Vlassara H.Recent progress in advanced glycation end products and diabetic complications[J].Diabetes,1997,46(Suppl.2):S 19-S25.
[54]Lyons TJ.Glycation and oxidation:a role in the pathogenesis of atherosclerosis[J].Am J Cardiol,1993,71(6):26B-31B.
[55]Beckman JA,Creager MA,Libby P.Diabetes and atherosclerosis:epidemiology,pathophysiology,and management[J].JAMA,2002,287(19):2570-2581.
[56]Taguchi S,Oinuma T,Yamada T.A comparative study of cultured smooth muscle cell proliferation and injury,utilizing glycated low density lipoproteins with slight oxidation,auto-oxidation,or extensive oxidation[J].J Atheroscler Thromb,2000,7(3):132-137.
[57]Chaturvedi N,Fuller JH,Pokras F,et al.Circulating plasma vascular endothelial growth factor and microvascular complications of type 1 diabetes mellitus:the influence of AGE inhibition[J].Diabet Med,2001,18(4):288-294.
[58]Walsh MF,Dominguez LJ, Sowers JR.Metabolic abnormalities in cardiac ischemia[J].Cardiol Clin,1995,13(4):529-538.
[59]Davi QCatalano I,Averna M,et al.Thromboxane biosynthesis and platelet function in type Ⅱ diabetes mellitus[J].N Engl Med,1990,322(25):1768-1774.
[60]Winocour PD,Bryszewska M,Watala C,et al.Reduced membrane fluidity in platelets from diabetic patients[J].Diabetes,1990,39(2):241-244.
[61]Standley PR,Ali S,Bapna C.Increased platelet cytosolic calcium responses to low density lipoprotein in type Ⅱ diabetes with and without hypertension[J].Am J Hypertens,1993,6(11 pt 1):938-943.
[62]Levy J,Gavin JR Ⅲ,Sowers JR.Diabetes mellitus:a disease of abnormal cellular calcium metabolism?[J].Am J Med,1994; 96(3):260-273.
[63]Fukuda K,Ozaki Y,Satoh K,et al.Phosphorylation of myosin light chain in resting platelets from NIDDM patients is enhanced:correlation with spontaneous aggregation[J].Diabetes,1997,46(3):588-593.
[64]Vinik AI,Erbas T,Park TS,et al.Platelet dysfunction in type 2 diabetes[J].Diabetes Care,2001,24(8):1476-1485.
[65]Sampietro T,Lenzi S,Cecchetti P,et al.Nonenzymatic glycation of human platelet membrane proteins in vitro and in vivo[J].Clin Chem,1986,32(7):1328-1331.
[66]Myllarniemi M,Calderon L,Lemstrom K,et al.Inhibition of platelet-derived growth factors receptor kinase inhibits vscular smooth muscle cell migration and proliferation[J].FASEB J,1997,11(13):1119-1126.
[67]Okuda Y,Adrogue HJ,Nakajima T,et al.Increased production of PDGF by angiotensin and high glucose in human vascular endothelium[J].Life Sci,1996,59(17):1455-1461.
[68]Jokl R,Colwell JA.Arterial thrombosis and atherosclerosis in diabetes[J].Diabetes Metab Rev,1997; 5:1-15.
[69]Tschoepe D,Rauch U,Schwippert B.Platelet-leukocyte-cross-talk in diabetes mellitus[J].Horm Metab Res,1997,29(12):631-635.
[70]Li Y,Woo V,Bose R.Platelet hyperactivity and abnormal Ca(2+) homeostasis in diabetes mellitus[J].Am J Physiol Heart Circ Physiol,2001,280(4):H1480-H1489.
[71]Garcia Frade LJ,de la Calle H,Alava I,et al.Diabetes mellitus as a hypercoagulable state:its relationship with fibrin fragments and vascular damage[J].Thromb Res,1987,47(5):533-540.
[72]Ford I,Singh TP,Kitchen S,et al. Activation of coagulation in diabetes mellitus in relation to the presence of vascular complications[J].Diabetes Med,1991,8(4):322-329.
[73]Carmassi F,Morale M,Puccetti R,et al.Coagulation and fibrinolytic system impairment in insulin dependent diabetes mellitus[J].Thromb Res,1992,67(6):643-654.
[74]Ceriello A,Quatraro A,Dellb Russo P,et al.Protein C deficiency in insulin-dependent diabetes:a hyperglycemia-related phenomenon[J].Thromb Haemost,1990,64(1):104-107.
[75]Cooper ME,Gilbert RE,Epstein M.Pathophysiology of diabetic nephropathy[J].Metabolism,1998,47(12 Suppl 1):3-6.
[76]The Diabetes Control and Complications Trail Research Group.The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus[J].N Engl J Med,1993,329(14):977-986.
[77]Tribe RM,Poston L.Oxidative stress and lipids in diabetes:a role in endothelium vasodilator dysfunction?[J] Vasc Med,1996,1(3):195-206.
[78]McMillan DE.Development of vascular complications in diabetesfJl. Vasc Med,1997,2(2):132-142.
[79]Baumgartner-Parzer SM,Wagner L,Pettermann M,et al.Modulation by high glucose of adhesion molecule expression in cultured endothelial cells[J].Diabetologia,1995,38(11):1367-1370.
[80]Brownlee M,Cerami A,Vlassara H.Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications[J].N Engl J Med,1988,318(20):1315-1321.
[81]Aronson D,Rayfield EJ.How hyperglycemia promotes atherosclerosis:molecular mechanisms[J].Cardiovasc Diabetol,2002,1:1.
[82]Vlassara H,Bucala R,Striker L.Pathogenic effects of advanced glycosylation:biochemical,biologic,and clinical implications for diabetes and aging[J].Lab Invest,1994,70(2):138-151.
[83]Brownlee M.Advanced protein glycosylation in diabetes and aging[J].Annu Rev Med,1995,46:223-234.
[84]Steinberg D.Low density lipoprotein oxidation and its pathobiological significance[J]. J Biol Chem,1997,272(34):20963-20966.
[85]Khoo JC,Miller E,McLoughlin P,et al.Enhanced macrophage uptake of low density lipoprotein after self-aggregation[J].Arteriosclerosis,1988,8(4):348-358.
[86]Ross R.Atherosclerosis-an inflammatory disease[J].N Engl J Med,1999,340(2):115-126.
[87]Griendling KK,Alexander RW.Oxidative stress and cardiovascular disease[J].Circulation,1997,96(10):3264-3265.
[88]Klein RL,Laimins M,Lopes-Virella MF.Isolation,characterization,and metabolism of the glycated and nonglycated subfractions of low-density lipoproteins isolated from type I diabetic patients and nondiabetic subjects[J].Diabetes,1995,44(9):1093-1098.
[89]Dzau VJ.Theodore Cooper Lecture:Tissue angiotensin and pathobiology of vascular disease,a unifying hypothesis[J].Hypertension,2001,37(4):1047-1052.
[90]Bucala R,Makita Z,Koschinsky T,et al.Lipid advanced glycosylation:pathway for lipid oxidation in vivo[J].Proc Natl Acad Sci USA,1993,90(14):6434-6438.
[91]Ferri C,Bellini C,Desideri G,et al.Plasma endothelin-1 level in obese hypertensive and normotensive man[J].Diabetes,1995,44(4):431-436.
[92]Hunter SJ,Garvey WT.Insulin action and insulin resistance:diseases involving defects in insulin receptors,signal transduction,and the glucose transport effector system[J].Am J Med,1998,105(4):331-345.
[93]Sowers JR,Sowers PS,Peuler JD.Role of insulin resistance and hyperinsulinemia in development of hypertension and atherosclerosis[J].J Lab Clin Med,1994,123(5):647-652.
[94]Reaven GM,Lithell H,Landsberg L.Hypertension and associated metabolic abnormalities-the role of insulin resistance and sympathoadrenal system[J].N Engl J Med,1996,334(6):374-381.
[95]McFarlane SI,Banerji M,Sowers JR.Insulin resistance and cardiovascular disease[J].J Clin Endocrinol Metab,2001,86(2):713-718.
[96]Meigs JB,D'Agostino RB Sr,Wilson PW,et al.Risk variable clustering in the insulin resistance syndrome.The Framingham offspring study[J].Diabetes,1997,46(10):1594-1600.
[97]Verma S,Wang CH,Li SH,et al.A self-fulfilling prophecy C-reactive protein attenuates nitric oxide production and inhibits angiogenesis[J].Circulation,2002,106(8):913-919.
[98]Gilbert RE,Rumble JR,Cao ZM,et al.Endothelin receptor antagonism ameliorates mast cell infiltration,vascular hypertrophy,and epidermal growth factor expression in experimental diabetes[J].Circ Res,2000,86(2):158-165.
[99]Bagdonaite L,Kucinskiene Z.Role of cytokines in cardiovascular disease[J].Seminars in Cardiology,2004,10(1):11-14.
[100]Tedgui A,Mallat Z.Anti-inflammatory mechanisms in the vascular wall[J].Circ Res,2001,88(9):877-887.
[101]Blake GJ,Ridker PM.Novel clinical markers of vascular wall inflammation[J].Cir Res,2001,89(9):763-771.
[102]Feener EP,King GL.Vascular dysfunction in diabetes mellitus[J].Lancet,1997,350(Suppl1):S19-S13.
[103]Koya D,King GL.Protein kinase C activation and the development of diabetic complications[J].Diabetes,1998,47(6):859-866.
[104]Park JY,Takahara N,Gabriele A,et al.Induction of endothelin-1 expression by glucose:an effect of protein kinase C activation[J].Diabetes,2000,49(7):1239-1248.
[105]Inaba T,Ishibashi S,Gotoda T,et al.Enhanced expression of platelet-derived growth factor-beta receptor by high glucose.Involvement of platelet-derived growth factor in diabetic angiopathy[J].Diabetes,1996,45(4):507-512.
[106]Blankenberg FQWen P,Zhu D,et al.Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabetic Zucker rats[J].Pediatr Radiol,2001,31(12):827-835.
[107]Tesfamariam B,Cohen RA.Free radicals mediate endothelial cell dysfunction caused by elevated glucose[J].Am J Physiol,1992,263 (2 pt 2):H321-H326.
[108]Giugliano D,Ceriello A,Paolisso G.Oxidative stress and diabetic vascular complications[J].Diabetes Care,1996,19(3):257-267.
[109]Vozarova B,Weyer C,Lindsay RS,et al.High white blood cell count is associated with a worsening of insulin sensitivity and predicts the development of type 2 diabetes[J].Diabetes,2002,51 (2):455-461.
[110]Hansen LK,Grimm RH Jr,Neaton JD.The relationship of white blood cell count to other cardiovascular risk factors [J].Int J Epidemiol,1990,19(4):881-888.
[111]Ernst E,Hammerschmidt DE,Bagge U,et al.Leukocytes and the risk of ischemic diseases[J].JAMA,1987,257(17):2318-2324.
[112]Glowacka E,Banasik M,Lewkowicz P,et al.The effect of LPS on neutrophils from the patients with high risks of type 1 diabetes mellitus in relation to IL-8、 IL-10 and IL-12 production and apoptosis in vitro[J].Scand J Immunol,2002,55(2):210-217.
[113]Fusman R,Rotstein R,Zeltser D,et al.The state of leukocyte adhesiveness/aggregation in the peripheral blood of patients with type 2 diabetes and ischemic vascular disease[J].Acta Diabetol,2001,38(1):43-49.
[114]Schieffer B,Schieffer E,Hilfiker-Kleiner D,et al.Expression of angiotensin Ⅱ and interleukin 6 in human coronary atherosclerotic plaques:potential implications for inflammation and plaque instability[J].Circulation,2000,101(12):1372-1378.
[115]Diet F,Pratt RE,Berry GJ,et al.Increased accumulation of tissue ACE in human atherosclerotic coronary artery disease[J].Circulation,1996,94(11):2756-2767.
[116]UK Prospective Diabetes Study(UKPDS)Group.Intensive blood-glucose control with sulphonylureas of insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes(UKPDS 33)[J].Lancet,1998;352:837-853.
[117]Brenner BM,Cooper ME,de Zeeuw D,et al,for the RENAAL Study Investigators.Effects of losartan on remal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy[J].N Engl J Med,2001,345(12):861-869.
[118]Lewis EJ,Hunsicker LG,Clarke WR,et al.for the Collaborative Study Group.Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes[J].N Engl J Med,2001,345(12):851-860.
[119]Parving HH,Lehnert H,Brochner-Mortensen J,et al.for the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group.The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes[J].N Engl J Med,2001,345(12):870-878.
[120]Heart Outcomes Prevention Evaluation Study Investigators.Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus:Results of the HOPE study and MICRO-HOPE substudy[J].Lancet,2000;355(9200):253-259.
[121]Jandeleit-Dahm KA,Tikellis C,Reid CM,et al. Why blockade of the rennin-angiotensin system reduces the incidence of new-onset diabetes[J].J Hypertens,2005,23(3):463-473.
[122]Dagenais GR,Yusuf S,Bourassa MG,et al.Effect of ramipril on coronary event in high-risk persons:result of the Heart Outcomes Prevention Evaluation study[J].Circulation,2001,104(5):522-526.
[123]方厚华,仇志华.糖尿病动物模型的研究进展[J].实验动物科学与管理,2004,18(2)：39-42.
[124]王宁,谢自敬,阿布力克木·吐尔地,等.糖尿病大鼠动脉粥样硬化与游离脂肪酸表达的关系[J].中国动脉硬化杂志,2005,13(5)：563-566.
[125]徐梓辉,周世文,钱桂生,等.2型糖尿病合并动脉粥样硬化大鼠模型的建立[J].中国病理生理杂志,2006,22(1)：205-208.
[126]陈丽萌,李学旺,黄利伟,等.2型糖尿病小鼠(KKAγ)动物模型的鉴定和早期肾脏病理改变[J].中国医学科学院学报,2002,24(1)：71-77.
[127]Cheng ZJ, Vaskonen T, Tikkanen I,et al. Endothelial dysfunction and salt-sensitive hypertension in spontaneously diabetic Goto-Kakizaki rats[J]. Hypertension,2001,37(2 Part 2):433-439.
[128]Ling ZC,Hong-Lie C,Ostenson CQet al.Hyperglycemia contributes to impaired insulin response in GK rat islets[J].Diabetes,2001;50(Suppl 1):S108-S112.
[129]Hughes SJ, Suzuki K, Goto Y. The role of islet secretory function in the development of diabetes in the GK Wistar rat[J]. Diabetologia,1994,37 (9):863-870.
[130]王宝金,代解杰.糖尿病动物模型的研究进展[J].上海实验动物科学,2003,23(2)：116-123.
[131]Zhao Q,Egashira K,Inoue S,et al.Vascular endothelial growth factor is necessary in the development of arteriosclerosis by recruiting/activating monocytes in a rat model of long-term inhibition of nitric oxide synthesis[J].Circulation,2002,105(9):1110-1115.
[132]Kataoka C,Egashira K,Ishibashi M,et al.Novel anti-inflammatory actions of amlodipine in a rat model of arteriosclerosis induced by long-term inhibition of nitric oxide synthesis[J].Am J Physiol Heart Circ Physiol,2004,286(2):H768-H774.
[133]Kataoka C,Egashira K,Inoue S,et al.Important role of Rho-kinase in the pathogenesis of cardiovascular inflammation and remodeling induced by long-term blockade of nitric oxide synthesis in rats[J].Hypertension,2002,39(2):245-250.
[134]Perrault LP,Malo O,Bidouard JP,et al.Inhibiting the NO pathway with intracoronary L-NAME infusion increases endothelial dysfunction and intimal hyperplasia after heart transplantation[J].J Heart Lung Transplant,2003,22(4):439-451.
[135]王芬,何华亮,张红敏,等.参芪复方对GK大鼠脂代谢异常的实验研究[J].天津中医药,2007,24(6)：507-508.
[136]谢毅强,李军茹,张红敏等.参芪复方治疗2型糖尿病胰岛素抵抗的临床研究[J].中华实用中西医杂志,2005,18(17)：844-846.
[137]张红敏,陈世伟,谢春光等.参芪复方对GK大鼠白色脂肪组织脂联素基因表达的影响[J].中成药,2006,28(7)：996-1001.
[138]张红敏,陈世伟,谢春光等.参芪复方抗自发性糖尿病GK大鼠早期动脉粥样硬化的作用机制[J].中国中药杂志,2006,31(15)：1272-1276.
[139]沈应君主编.中药药理学[M].人民卫生出版社,2000：96-97.
[140]Van de Ree MA, Huisman MV, Princen HM. Strong decrease of high sensitively C-reactive protein with high-dose atorvastatin in patients with type 2 diabetes mellitus[J]. Atherosclerosis,2003,166(1):129-135.
[141]Topol EJ. Intensive statin therapy-a sea change in cardiovascular prevention. N Engl J Med,2004,350(15):1562-1564.
[142]Auer J, Berent R, Weber T, et al. Clinical significance of pleiotropic effects of statins:lipid reduction and beyond[J].Curr Med Chem,2002,9(20):1831-1850.
[143]Lind L.Circulating markers of inflammation and atherosclerosis [J].Atherosclerosis,2003,169(2):203-214.
[144]Yuan M,Konstantopoulos N,Lee J,et al.Reversal of obesity-and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta[J].Science,2001,293(5535):1673-1677.
[145]Greenberg AS. The expanding scope of the metabolic syndrome and implications for the management of cardiovascular risk in type 2 diabetes with particular focus on the emerging role of the thiazolidinediones [J].J Diabetes Complications,2003,17(4):218-228.
[146]Dandona P, Aljada A,Mohanty P,et al.Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subiects:evidence for an anti-inflammatory effect[J]?J Clin Endocrinol Metab,2001,86(7):3257-3265.
[147]杨宝峰,苏定冯,周宏灏.《药理学》[M].第七版.北京.人民卫生出版社,2008：264-267.
[148]Cannon CP,Braunwald E,McCabe CH,et al.Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 investigatiors.Intensive versus moderate lipid lowering with statins after acute coronary syndromes(PROVE-IT Study) [J].N Engl J Med,2004,350(15):1495-1504.
[149]Stepp DW,Ou J,Ackerman AW,et al.Native LDL and minimally oxidized LDL differentially regulate superoxide anion in vascular endothelium in situ[J].Am J Physiol Heart Circ Physiol,2002,283(2):H750-759.
[150]Ou J,Ou Z,Jones DW,et al.L-4F,an apolipoprotein A-1 mimetic,dramatically improves vasodilation in hypercholesterolemia and sickle cell disease [J].Circulation,2003,107(18):2337-2341.
[151]Mason RP,Walter MF,Jacob RF.Effects of HMG-CoA reductase inhibitors on endothelial function:role of microdomains and oxidative stress [J].Circulation,2004,109(Suppl1):Ⅱ34-41.
[152]Bruemmer D,Yin F,Liu j,et al.Atorvastatin inhibits expression of minichromosome maintenance proteins in vascular smooth muscle cells[J].Eur Pharmacol,2003,462(1-3):15-23.
[153]Libby P,Aikawa M.Mechanisms of plaque stabilization with statins[J].Am J Cardiol,2003,91 (4A),4B-8B.
[154]Bea F,Blessing E,Bennett B,et al.Simvastatin promotes atherosclerotic plaque stability in apoE-deficient mice independently of lipid lowering[J].Arterioscler Thromb Vasc Biol,2002,22(11):1832-1837.
[155]Backes JM,Howard PA,Moriarty PM.Role of C-reactive protein in cardiovascular disease[J].Ann Pharmacother,2004,38(1):110-118.
[156]Horne BD,Muhlestein JB,Carlquist JF,et al.Intermoutain Heart Collaborative(IHC) Study Group:Statin therapy interacts with cytomegalovirus seropositivity and high C-reactive protein in reducing mortality among patients with angiographically significant coronary disease[J].Circulation,2003,107(2):258-263.
[157]Bonetti PO,Lerman LO,Napoli C,et al.Statin effects beyond lipid lowering-are they clinically relevant[J]?Eur Heart J,2003,24(3):225-248.
[158]Rezaie-Majd A,Prager GW,Bucek RA,et al.Simvastatin reduces the expression of adhesion molecules in circulating monocytes from hypercholesterolemic patients [J].Arterioscler Thromb Vasc Biol,2003,23(3):397-403.
[159]Weitz-Schmidt G,Welzenbach K,Brinkmann V,et al.Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site[J].Nat Med,2001,7(6):687-692.
[160]Sposito AC,Chapman MJ.Statin therapy in acute coronary syndromes:mechanistic insight into clinical benefit[J].Arterioscler Thromb Vasc Biol,2002,22(10):1524-1534.
[161]Saijonmaa O,Nyman T,Fyhrguist F.Atorvastatin inhibits angiotensin-converting enzyme induction in differentiating human marophages[J].Am J Physiol Heart Circ Physiol,2007,292(4):H1917-1921.
[162]Ito T,Ikeda U,Yamamoto K,et al.Regulation of interleukin-8 expression by HMG-CoA reductase inhibitors in human vascular smooth muscle cells[J].Atherosclerosis,2002,165(1):51-55.
[163]Landsberger M, Wolff B,Jantzen F,et al.Cerivastatin reduces cytokine-induced surface expression of ICAM-1 via increased shedding in human endothelial cells[J].Atherosclerosis,2007,190(1):43-52.
[164]Nickenig G,Baumer AT,Temur Y,et al.Statin-sensitive dysregulated AT1 receptor function and density in hypercholesterolemic men [J].Circulation,1999,100(21):2131-2134.
[165]Seljeflot I,Tonstad S,Hjermann I,et al.Reduced expression of endothelial cell markers after 1 year treatment with simvastatin and atorvastatin in patients with coronary heart disease[J].Atherosclerosis,2002,162(1):179-185.
[166]Heart Protection Study Collaborative Group.MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals:a randomised placebo-controlled trial[J].Lancet,2002,360(9326):7-22.
[167]Colhoun HM,Betteridge DJ,Durrington PN,et al.Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study(CARDS):Multicentre randomised placebo-controlled trial.Lancet,2004,364(9435):685-696.
[168]黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算[J].中国临床药理学与治疗学,2004,9(9)：1069-1072.
[169]李稻主编.医学功能学科—实验原理与方法[M].人民卫生出版社,北京：2008,33-35.
[170]Barzilay JI,Abraham L,Heckbert SR,et al.The relation of markers of inflammation to the development of glucose disorders in the elderly:the Cardiovascular Health Study[J].Diabetes,2001,50(10):2384-2389.
[171]Festa A,DAgostino RJ,Howard Qet al.Chronic subclinical inflammation as part of the insulin resistance syndrome:the Insulin Resistance Atherosclerosis Study(IRAS)[J].Circulation,2000,102(1):42-47.
[172]Visser M,Bouter LM,Mc Quillan GM,et al.Elevated C-reactive protein levels in overweight and obese adults[J].JAMA,1999,282(22):2131-2135.
[173]Ridker PM,Cushman M,Stampfer MJ,et al.Inflammation,aspirin and risk of cardiovascular disease in apparently health men[J].N Engl J Med,1997,336(14):973-979.
[174]Fiordaliso F,Leri A,Cesselli D,et al.Hyperglycemia activates p53 and p53-regulated genes leading to myocyte cell death[J].Diabetes,2001;50(10):2363-2375.
[175]Leri A,Claudio PP,Li Q,et al.Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell[J].J Clin Invest,1998,101(7):1326-1342.
[176]Leri A,Liu Y,Wang X,et al.Overexpression of insulin-like growth factor-1 attenuates the myocyte renin-angiogensin system in transgenic mice[J].Circ Res,1999,84(7):752-762.
[177]Leri A,Fiordaliso F,Setoguchi M,et al.Inhibition of p53 function prevents renin-angiotensin system activation and stretch-mediated myocyte apoptosis[J].Am J Pathol,2000,157(3):843-857.
[178]He W,Miao FJ,Lin DC,et al.Critic acid cycle intermediates as ligands for orphan G-protein-coupled receptors[J].Nature,2004,429(6988):188-193.
[179]Toma I,Kang JJ,Sipos A,et al.Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney[J].J Clin Invest,2008,118(7):2526-2534.
[180]Rajagopalan S,Harrison DGReversing endothelial dysfunction with ACE inhibitors:A new TREND[J].Circulation,1996,94(3):240-243.
[181]曾朝荣,兰永乔.动脉内皮与心血管疾病[J].中国心血管病杂志,2001,6(1)：47-50.
[182]Rajagopalan S,Kurz S,Munzel T,et al.Angiotensin Ⅱ-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation:Contribution to alternation of vasomotor tone[J].J Clin Invest,1996,97(8):1916-1923.
[183]Harrison DG,Cai H.Endothelial control of vasomotion and nitric oxide production.Cardiol Clin,2003,21(3):289-302.
[184]景涛,何国祥,刘建平,等.血管紧张素Ⅱ对血管平滑肌细胞粘着斑及肌动蛋白细胞骨架组装的影响及意义[J].第三军医大学学报.2001,10(23)：1173-1176.
[185]Rubin P,Williams J P,Riggs P N,et al.Cellular and molecular mechanisms of radiation inhibition of restenosis.Part Ⅰ:role of the macrophage and platelet-derived growth factor[J].Int J Radiat Oncol Biol Phys,1998,40(4):929-941.
[186]Sironi L,Calvio AM,Arnaboldi L,et al.Effect of valsartan on angiotensin II-induced plasminogen activator inhibitor-1 biosynthesis in arterial smooth muscle cells[J].Hypertension,2001,37(3):961-966.
[187]Labinjoh C,Newby DE,Dawson P,et al.Fibrinolytic actions of intra-arterial angiotensin II and bradykinin in vivo in man[J].Cardiovasc Res,2000,47(4):707-714.
[188]Lusis AJ,Atherosclerosis[J].Nature,2000,407(6801):233-241.
[189]Morawietz H,Rueckschloss U.Angiotensin Ⅱ induces LOX-1,the human endothelial receptor for oxidized low-density lipoprotein[J].Circulation,1999,100(9):899-902.
[190]Touyz RM.Molecular and cellular mechanisms in vascular injury in hypertension:role of angiotensin Ⅱ [J].Curr Opin Nephrol Hypertens,2005,14(2):125-131.
[191]Kranzhfer R,Browatzki M,Schmidt J,et al.Angiotensin Ⅱ activates the proinflammatory transcription factor nuclear factor-kappaB in human monocytes[J].Biochem Biophys Res Commun,1999,257(3):826-828.
[192]Pueyo ME,Gonzalez W,Nicoletti A,et al.Angiotensin Ⅱ stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor-kappaB activation induced by intracellular oxidative stress[J].Arterioscler Thromb Vasc Biol,2000,20(3):645-51.
[193]Tham DM,Maetin-Mcnulty B,Wang YX,et al.Angiotensin Ⅱ is associated with activation of NF-к B-mediated genes and downregulation of PPARs[J].Physiol Genomics,2002,11(1):21-36.
[194]Kato H,Suzuki H,Tajima S,et al.Angiotensin Ⅱ stimulates collagen synthesis in cultured vascular smooth muscle cells[J].J Hypertens,1991,9(1):17-22.
[195]Mifune M,Sasamura H,Shimizu-Hirota R,et al.Angiotensin II type 2 receptors stimulate collagen synthesis in cultured vascular smooth muscle cells[J].Hypertension,2000,36(5):845-850.
[196]Ju H,Dixon IM.Extracellular matrix arid cardiovascular diseases[J].Can J Cardiol,1996,12(12):1259-1267.
[197]Iozzo RV.Matrix proteoglycans:from molecular design to cellular function[J].Annu Rev Biochem,1998,67:609-652.
[198]Sasamura H,Shimizu-Hirota R,Nakaya H,Saruta T.Effect of ATI receptor antagonist on proteoglycan gene expression in hypertensive rats[J].Hypertens Res,2001,24(2):165-172.
[199]Moriguchi Y,Matsubara H,Mori Y,et al.Angiotensin Ⅱ-induced transactivation of epidermal growth factor receptor regulates fibronectin and transforming growth factor-beta synthesis via transcriptional and posttranscriptional mechanisms[J].Circ Res,1999,84(9):1073-1084.
[200]Libby P,Lee RT.Matrix matters[J].Circulation,2000,102(16):1874-1876.
[201]Chen X,Li W,Yoshida H,et al.Targeting deletion of angiotensin type 1B receptor gene in the mouse[J].Am J Physiol,1997,272(3 pt 2):F299-F304.
[202]Bonnardeaux A,Davies E,Jeunemaitre X,et al.Angiotensin Ⅱ type 1 receptor gene polymorphisms in human essential hypertension[J].Hypertension,1994,24(1):63-69.
[203]Benetos A,Topouchian J,Ricard S,et al.Influence of angiotensin Ⅱ type 1 receptor polymorphism on aortic stiffness in never-treated hypertensive patients[J].Hypertension,1995;26(1):44-47.
[204]Berge KE,Bakken A,Bohn M,et al.A DNA polymorphism at the angiotensin Ⅱ type 1 receptor(AT1R) locus and myocardial infarction[J].Clin Genet,1997,52(2):71-76.
[205]AbdAlla S,Lother H,Abdel-tawab AM,et al.The angiotensin Ⅱ. AT2 receptor is an AT1 receptor antagonist[J].J Biol Chem,2001,276(43):39721-39726.
[206]Hansen JL,Theilade J,Haunso S,et al.Oligomerization of wild type and nonfunctional mutant angiotensin Ⅱ type Ⅰ receptors inhibits galphaq protein signaling but not ERK activation[J].J Biol Chem,2004,279(23):24108-24115.
[207]Barki-Harrington L,Luttrell LM,Rockman HA.Dual inhibition of beta-adrenergic and angiotensin Ⅱ receptors by a single antagonist:a functional role for receptor-receptor interaction in vivo[J].Circulation,2003,108(13):1611-1618.
[208]Touyz RM,He G,Deng LY,et al.Role of extracellular signal-regulated kinases in angiotensin Ⅱ-stimulated contraction of smooth muscle cells from human resistance arteries[J].Circulation,1999,99(3):392-399.
[209]Mehta PK,Griendling KK.Angiotensin Ⅱ cell signaling:physiological and pathological effects in the cardiovascular system[J].Am J Physiol Cell Physiol,2007,292(1):C82-C97.
[210]Nickenig G,Jung O,Strehlow K,et al.Hypercholesterolemia is associated with enhanced angiotensin AT1-receptor expression[J].Am J Physiol,1997,272(6 pt 2):H2701-2707.
[211]Nickenig G,Sachinidis A,Michaelsen F,et al.Upregulation of vascular angiotensin Ⅱ receptor gene expression by low-density lipoprotein in vascular smooth muscle cells[J].Circulation,1997,95(2):473-478.
[212]Griendling KK,Lassegue B,Alexander RW.Angiotensin recepors and their therapeutic implications[J]. Annu Rev Pharmacol Toxicol,1996,36:281-306.
[213]Mukoyama M,Nakajima M,Horiuchi M,et al.Expression cloning of type 2 angitensin Ⅱ receptor reveals a unique class of seven-transmembrane receptors[J].J Biol Chem,1993,268(33):24539-24542.
[214]Shanmugam S,Corvol P,Gasc JM.Angiotensin Ⅱ type 2 receptor mRNA expression in the developing cardiopulmonary system of the rat[J].Hypertension,1996,28(1):91-97.
[215]Tsutsumi Y,Matsubara H,Ohkubo N,et al. Angiotensin Ⅱ type 2 receptor is upregulated in human heart with interstitial fibrosis,and cardiac fibroblasts are the major cell type type for its expression[J].Circ Res,1998,83(10):1035-1046.
[216]Bedecs K,Elbaz N,Sutren M,et al.Angiotensin Ⅱ type 2 receptors mediate inhibition of mitogen-activated protein kinase cascade and functional activation of SHP-1 tyrosine phosphatase[J].Biochem J,1997,325(pt 2):449-454.
[217]Munzenmaier DH,Greene AS.Opposing action of angiotensin Ⅱ on microvascular growth and arterial blood pressure[J].Hypertension,1996,27(3 pt 2):760-765.
[218]Bumpus FM,Catt KJ,Chiu AT,et al.Nomenclature for angiotensin receptors. A report of the Nomenclature Committee of the Council for High Blood Pressure Research[J].Hypertension,1991,17(5):720-721.
[219]Jobin C,Hellerbrand C,Licato LL,et al.Mediation by NF-kappa B of cytokine induced expression of intercellular adhesion molecule 1(ICAM-1) in a intestinal epithelial cell line,a process blocked by proteasome inhibitors[J].Gut,1998,42(6):779-787.
[220]Roebuck KA,Finnegan A.Regulation of intercellular adhesion molecule-1 (CD54) gene expression[J].J Leukoc Biol,1999,66(6):876-888.
[221]Wissink S,van de Stolpe A,Caldenhoven E,et al.NF-kappa B/Rel family members regulating the ICAM-1 promoter in monocytic THP-1 cells[J].Immunobiology,1997,198(1-3):50-64.
[222]Osborn L,Hession C,Tizard R,et al.Direct expression cloning of vascular cell adhesion molecule 1,a cytokine-induced endothelial protein that binds to lymphocytes[J].Cell,1989,59(6):1203-1211.
[223]Paine R 3rd,Ward PA.Cell adhesion molecules and pulmonary fibrosis[J].Am J Med,1999,107(3):268-279.
[224]Macphee CH,Nelson JJ,Zalewski A.Lipoprotein-associated phosphlipase A2 as a target of therapy[J].Curr Opin Lipidol,2005,16(4):442-446.
[225]Karabina SA,Brocheriou I,Le Naouy Qet al.Atherogenic properties of LDL particles modified by human group X secreted phospholipase A2 on human endothelial cell function[J].FASEB J,2006,20(14):2547-2549.
[226]O'Brien KD,McDonald TO,Chait A,et al.Neovascular expression of E-selectin,intercellular adhesion molecule-1,and vascular cell adhesion molecule-1 in human atherosclerosis and their relation to intimal leukocyte content[J].Circulation,1996,93(4):672-682.
[227]Cybulsky MI,Iiyama K,Li H,et al.A major role for VCAM-l,but not ICAM-1,in early atherosclerosis[J].J Clin Invest,2001,107(10):1255-1262.
[228]Costanzo A,Moretti F,Burgio V,et al.Endothelial activation by angiotensin Ⅱ through NFkappaB and p38 pathways:Involvment of NFkappaB-inducible kinase (NIK),free oxygen radicals,and selective inhibition by aspirin[J].J Cell Physiol,2003,195(3):420-410.
[229]张红敏,陈世伟,谢春光,等.参芪复方对GK大鼠炎症标志物的影响及机理探讨[J].中药材,2006,29(3)：249-253.
1 Ruschitzka FT,Noll QLuscher TF.The endothelium in coronary artery disease[J].Cardiology,1997,88 Suppl 3:3-19.
2 Rajagopalan S,Harrison D G.Reversing endothelial dysfunction with ACE inhibitors:A new trend[J].Circulation,1996,94(3):240-243.
3曾朝荣,兰永乔.动脉内皮与心血管疾病[J].中国心血管病杂志,2001,6(1)：47-50.
4 Rajagopalan S,Kurz S,Munzel T,et al.Angiotensin Ⅱ-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation:Contribution to alternation of vasomotor tone[J].J Clin Invest,1996,97(8):1916-1923.
5 Harrison DG,Cai H.Endothelial control of vasomotion and nitric oxide production[J].Cardiol Clin,2003,21(3):289-302.
6 Kuroski de Bold ML.Estrogen,natriuretic peptides and the renin-angiotensin system[J].Cardiovasc Res,1999,41 (3):524-531.
7 Itoh H,Mukoyama M,Pratt RE,et al.Multiple autocrine growth fators modulate vascular smooth muscle cells growth response to angiotensin-Ⅱ [J].J Clin Invest,1993,91 (5):2268-2274.
8郭涛,任大宏.ANG-Ⅱ、ANP对培养的人血管内皮细胞bFGF表达的影响[J].中国组织化学与细胞化学杂志,2002,11(3)：319-322.
9任大宏,曾晓坤.自发性高血压大鼠高血压进展期肠系膜动脉的超微结构变化[J].同济医科大学学报.1998,27(6)：417-419.
10 Mulvany MJ, Vascular remodelling of resistance vessels:can we define this[J]?Cardiovasc Res,1999,41 (1):9-13.
11 Rubin P,Williams J P,Riggs P N,et al.Cellular and molecular mechanisms of radiation inhibition of restenosis.Part Ⅰ:role of the macrophage and platelet-derived growth factor[J].Int J Radiat Oncol Biol Phys,1998,40(4):929-941.
12 Cary LA,Guan J L.Focal adhesion kinase in integrin-mediated signaling[J].Front Biosci,1999,4(3):D102-113.
13 Castellano F,Montcourrier P,Guillenmot J C,et al.Inducible recruitment of Cdc42 or WASP to a cell-surface receptor triggers actin polymerization and filopodium formation [J].Curr Biol,1999,9(7):351-360.
14景涛,何国祥,刘建平,等.血管紧张素Ⅱ对血管平滑肌细胞粘着斑及肌动蛋白细胞骨架组装的影响及意义[J].第三军医大学学报.2001,10(23)：1173-1176.
15 Folsom AR.Fibrinolytic factors and atherothrombotic events:epidemiological evidence[J]. Ann Med,2000,32 suppl 1:85-91.
16 Sironi L,Calvio AM,Arnaboldi L,et al.Effect of valsartan on angiotensin Ⅱ-induced plasminogen activator inhibitor-1 biosynthesis in arterial smooth muscle cells[J].Hypertension,2001,37(3):961-966.
17 Labinjoh C,Newby DE,Dawson P,et al.Fibrinolytic actions of intra-arterial angiotensin Ⅱ and bradykinin in vivo in man.Cardiovasc Res,2000,47(4):707-714.
18 Lusis AJ, Atherosclerosis[J].Nature,2000,407(6801):233-241.
19 Morawietz H,Rueckschloss U. Angiotensin Ⅱ induces LOX-1,the human endothelial receptor for oxidized low-density lipoprotein[J].Circulation,1999,100(9):899-902.
20 Uehara Y,Urata H,Sasaguri M,et al.Increased chymase activity in internal thoracic artery of patients with hypercholesterolemia[J].Hypertension,2000,35 (1 Pt 1):55-60.
21 Suzuki Y,Ruiz-Ortega M,Lorenzo O,et al.Inflammation and angiotensin Ⅱ[J]. Int J Biochem Cell Biol,2003,35(6):881-900.
22车在前,等.血管紧张素Ⅱ诱导血管外膜成纤维细胞产生结缔组织生长因子.高血压杂志,2005,5(13)：301-305.
23 Touyz RM.Molecular and cellular mechanisms in vascular injury in hypertension:role of angiotensin Ⅱ.Curr Opin Nephrol Hypertens,2005,14(2):125-131.
24 Kranzhfer R,Browatzki M,Schmidt J,et al.Angiotensin Ⅱ activates the proinflammatory transcription factor nuclear factor-kappaB in human monocytes[J].Biochem Biophys Res Commun,1999,257(3):826-828.
25 Pueyo ME,Gonzalez W,Nicoletti A,et al.Angiotensin Ⅱ stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor-kappaB activation induced by intracellular oxidative stress[J].Arterioscler Thromb Vasc Biol,2000,20(3):645-51.
26 Tham DM,Maetin-Mcnulty B,Wang YX,et al.Angiotensin Ⅱ is associated with activation of NF-к B-mediated genes and downregulation of PPARs[J].Physiol Genomics,2002,11(1):21-30.
27 Arenas IA,Xu Y,Lopez-Jaramillo P,et al.Angiotensin Ⅱ-induced MMP-2 release from endothelial cells is mediated by TNF-alpha[J].Am J Physiol cell Physiol,2004,286(4):C779-C784.
28 Kalra D,Sivasubramanian N,Mann DL.Angiotensin Ⅱ induces tumor necrosis factor biosynthesis in the adult mammalian heart through a protein kinase-dependent pathway[J].Circulation,2002,105(18):2198-2205.
29 Kato H,Suzuki H,Tajima S,et al.Angiotensin Ⅱ stimulates collagen synthesis in cultured vascular smooth muscle cells[J].J Hypertens,1991,9(1):17-22.
30 Mifune M,Sasamura H,Shimizu-Hirota R,et al.Angiotensin Ⅱ type 2 receptors stimulate collagen synthesis in cultured vascular smooth muscle cells[J].Hypertension,2000,36(5):845-850.
31 Ju H,Dixon IM.Extracellular matrix and cardiovascular diseases[J].Can J Cardiol,1996,12(12):1259-1267.
32 Iozzo RV.Matrix proteoglycans:from molecular design to cellular function[J].Annu Rev Biochem,1998,67:609-652.
33 Sasamura H,Shimizu-Hirota R,Nakaya H,Saruta T.Effect of AT1 receptor antagonist on proteoglycan gene expression in hypertensive rats[J].Hypertens Res,2001,24(2):165-172.
34 Moriguchi Y,Matsubara H,Mori Y,et al.Angiotensin Ⅱ-induced transactivation of epidermal growth factor receptor regulates fibronectin and transforming growth factor-beta synthesis via transcriptional and posttranscriptional mechanisms[J].Circ Res,1999,84(9):1073-1084.
35 Libby P,Lee RT.Matrix matters[J].Circulation,2000,102(16):1874-1876.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |