白芍总苷对糖尿病大鼠肾组织氧化应激的影响
|
摘要
背景与目的DN已成为ESRD的主要病因之一,其发生与发展的内在机制尚未完全阐明。近年研究表明,氧化应激在糖尿病并发症包括DN的发生和发展中起重要作用,应用抗氧化剂可有效延缓DN的进展。TGP是中药白芍根中提取的有效成分,它主要含有芍药苷、羟基芍药苷、芍药花苷、芍药内酯苷及苯甲酰芍药苷等,具有抗炎、抗氧化和免疫调节等活性。我们既往的研究表明,TGP对DN具有明显保护作用,但不降低血糖和血脂的水平。本研究进一步观察TGP对实验性糖尿病大鼠肾脏氧化应激的影响,以探讨其抗DN的作用机制。
方法应用链脲佐菌素诱导大鼠糖尿病模型,随机分:正常组、模型组、TGP给药组。TGP按50,100,200mg·kg~(-1)不同剂量每日灌胃给药,对照组和糖尿病组给予等量溶媒。所有大鼠在整个实验期间喂标准饮食,自由饮水,不应用胰岛素,观察8wk。血糖由全自动生化分析仪检测,PAS染色对肾组织作病理形态学检查同时采用彩色病理图像分析系统测定肾小球平均容积V_G,TⅡ,肾组织T-AOC,SOD,CAT和GSH-PX活性由分光光度法检测,肾组织NT蛋白的表达采用Western印迹方法检测,肾小管-间质OPN,α-SMA表达采用免疫组化方法检测。
结果1.各组大鼠一般指标变化与对照组相比,糖尿病模型组大鼠表现为血糖升高、体重下降、相对肾重(肾重/体重)增加(P＜0.05,P＜0.01),TGP(50,100,200mg·kg~(-1))给药8wk没有防止模型组大鼠血糖升高与体重下降。TGP(50,100,200mg·kg~(-1))给药组大鼠相对肾重与模型组相比有所下降,但差异无统计学意义。2.各组大鼠肾脏病理形态学变化模型组大鼠V_G与TⅡ明显高于对照组,TGP 50mg·kg~(-1)给药组大鼠V_G明显低于模型组,TⅡ较模型组有所下降,但差异未达统计学意义,TGP 100,200mg·kg~(-1)给药组V_G与TⅡ均明显低于模型组(P＜0.05,P＜0.01)。3.肾组织T-AOC,SOD,CAT和GSH-PX活性变化与正常对照组比较,糖尿病模型组大鼠肾组织T-AOC,SOD与CAT活性明显降低(P＜0.01),GSH-PX活性无明显变化;TGP 200mg·kg~(-1)给药8wk肾组织T-AOC、SOD与CAT活性均明显高于模型组(P＜0.05,P＜0.01),对GSH-PX活性无明显影响。4.各组大鼠肾组织NT蛋白表达变化Western印迹结果表明,糖尿病模型组肾组织NT蛋白表达较正常对照组增加3.4倍,TGP 50,100和200 mg·kg~(-1)给药8wk后肾组织NT蛋白表达与模型组相比分别下降41.2%、43.8%和57.5%。5.各组大鼠肾小管-间质OPN蛋白、α-SMA蛋白表达变化免疫组化显示照组大鼠肾小管-间质有微弱OPN蛋白表达,模型组肾小管-间质OPN与α-SMA蛋白表达明显高于对照组(p＜0.01),TGP 100,200mg·kg~(-1)给药组肾小管-间质OPN表达明显低于模型组(p＜0.01)。免疫组化显示对照组大鼠肾小管-间质有微弱α-SMA蛋白表达,模型组。肾小管-间质α-SMA蛋白表达明显高于对照组(p＜0.01),TGP 50,100,200mg·kg~(-1)给药组肾小管-间质α-SMA蛋白表达明显低于模型组(p＜0.01)。
结论糖尿病大鼠肾脏存在氧化应激反应,TGP抗糖尿病肾病的作用可能与其抗氧化活性有关。
Background and objective Diabetic nephropathy(DN) has become one of the main cause of end-stage renal disease(ESRD),but unfortunately the intimate mechanisms leading to the development and progression of renal injury are not yet fully known.The recent study in vivo and in vitro evidence demonstrated that oxidative stress play a major role in the development and progression of diabetic nephropathy,and that antioxidant treatment had significant protective effects on DN.Total glucosides of paeony(TGP) are active compounds extracted from the roots of the tradition herb Paeonia lactiflora Pall,its mainly composed of peoniflorin,hydroxide radical peoniflorin, peonin,albiflorin and benzoylpaeoniflorin.It possesses a variety of pharmacological functions,including anti-inflammation,anti-oxidative stress and immunoregulatory activity. The purpose of the present study was to investigate the effects of TGP on Oxidative stress in renal tissue of diabetic rats induced by STZ and explore the possible mechanism.
Methods Fifty adult male Sprague-Dawley rats were separated into five groups at random.Control group(n=10),model group(n=10),model group treated with TGP 50 mg·kg~(-1)(n=10),model group treated with TGP 100 mg·kg~(-1)(n=10) and model group treated with TGP 200 mg·kg~(-1)(n=10).To induce an experimental model of diabetes, rats received a single intraperitoneal injection of STZ(60mg·kg~(-1) d~(-1)).TGP was given by gavage.8 weeks after STZ injection,the following determinations were done in samples:(1) BG were determined according to standard methods;(2) Renal lesions were evaluated using PAS staining,the mean glomerular volume(V_G) and indices for tubulointerstitial injury(TII) were measured by using pathology image analysis system software;(3) Renal tissue T-AOC,GSH-PX,CAT,SOD were determined by spectrophotometric method;(4) Expression of nitrotyrosine(NT) was measured by Western blot analysis;(5) Expression of osteopontin(OPN) andα-smooth muscle actin (α-SMA) in renal tubulointerstitium were determined by immunohistochemistry method.
Results 1.BG,Body weight(BW) ratio of KW to BW(KW/BW):8 weeks after STZ injection,there was a significant increase in BG(P＜0.01) and significantly decreased in BW(p＜0.01) in diabetic rats compared with control group.The BG level of TGP group(50mg,100mg and200mg·kg~(-1)) have no statistically significant difference compared with model group.KW/BW in TGP group(50mg,100mg and 200mg·kg~(-1)) was decreased compared with model group,but there have no statistically significant.2. Renal pathologic morphology:Compared with control group,V_G and TII in model group was significantly increased.V_G in TGP group(50mg·kg~(-1)) was significantly lower than model group(P＜0.05),TII in TGP group(50mg·kg~(-1)) was lower than model group,but there have no statistically significant.V_G and TII in TGP group(100,200mg·kg~(-1)) was significantly lower than model group(P＜0.05,P＜0.01).3.T-AOC,
GSH-PX,CAT,SOD activities in renal tissue:The T-AOC,SOD and CAT activities in renal tissue of model group significantly decreased compared with that of control group(P＜0.01).TGP treatment with 200mg·kg~(-1) increased the T-AOC,SOD and CAT activities(P＜0.01,P＜0.05).In addition,GSH-PX have no difference between control group,model group,and TGP group(50,100,200mg·kg~(-1)).4.NT expression in renal tissue:Western blot analysis noted that the expression of NT protein in ranal tissue of model group increased by 3.4 folds to that of control group,TGP treatment with 50,100 and 200mg.kg~(-1) reduced the increased expression of NT protein by 41.2%,43.8%and 57.5%,respectively.5.OPN andα-SMA protein expression in renal tubulointerstitium:There was minimal immunohistohemistrical staining for OPN in renal tubulointerstitium of control group rats.Immunostaining for OPN was markedly increased in model group in tubulointerstitium(P＜0.01),elevated expression of OPN protein in renal tubulointerstitium in diabetic rats were only significantly inhibited by TGP treatment with 100 and 200mg.kg~(-1)(p＜0.01).There was minimal immunohistohemistrical staining forα-SMA in renal tubulointerstitium of control group rats.Immunostaining forα-SMA was markedly increased in model group in tubulointerstitium(P＜0.01),and increased expression ofα-SMA protein were significantly inhibited by TGP treatment with 50,100 and 200mg.kg~(-1)(p＜0.01).
Conclusion The oxidative stress is increased in the diabetic rat kidney,and TGP can prevent renal damage associated with diabetes by attenuating the oxidative stress.
方法应用链脲佐菌素诱导大鼠糖尿病模型,随机分:正常组、模型组、TGP给药组。TGP按50,100,200mg·kg~(-1)不同剂量每日灌胃给药,对照组和糖尿病组给予等量溶媒。所有大鼠在整个实验期间喂标准饮食,自由饮水,不应用胰岛素,观察8wk。血糖由全自动生化分析仪检测,PAS染色对肾组织作病理形态学检查同时采用彩色病理图像分析系统测定肾小球平均容积V_G,TⅡ,肾组织T-AOC,SOD,CAT和GSH-PX活性由分光光度法检测,肾组织NT蛋白的表达采用Western印迹方法检测,肾小管-间质OPN,α-SMA表达采用免疫组化方法检测。
结果1.各组大鼠一般指标变化与对照组相比,糖尿病模型组大鼠表现为血糖升高、体重下降、相对肾重(肾重/体重)增加(P＜0.05,P＜0.01),TGP(50,100,200mg·kg~(-1))给药8wk没有防止模型组大鼠血糖升高与体重下降。TGP(50,100,200mg·kg~(-1))给药组大鼠相对肾重与模型组相比有所下降,但差异无统计学意义。2.各组大鼠肾脏病理形态学变化模型组大鼠V_G与TⅡ明显高于对照组,TGP 50mg·kg~(-1)给药组大鼠V_G明显低于模型组,TⅡ较模型组有所下降,但差异未达统计学意义,TGP 100,200mg·kg~(-1)给药组V_G与TⅡ均明显低于模型组(P＜0.05,P＜0.01)。3.肾组织T-AOC,SOD,CAT和GSH-PX活性变化与正常对照组比较,糖尿病模型组大鼠肾组织T-AOC,SOD与CAT活性明显降低(P＜0.01),GSH-PX活性无明显变化;TGP 200mg·kg~(-1)给药8wk肾组织T-AOC、SOD与CAT活性均明显高于模型组(P＜0.05,P＜0.01),对GSH-PX活性无明显影响。4.各组大鼠肾组织NT蛋白表达变化Western印迹结果表明,糖尿病模型组肾组织NT蛋白表达较正常对照组增加3.4倍,TGP 50,100和200 mg·kg~(-1)给药8wk后肾组织NT蛋白表达与模型组相比分别下降41.2%、43.8%和57.5%。5.各组大鼠肾小管-间质OPN蛋白、α-SMA蛋白表达变化免疫组化显示照组大鼠肾小管-间质有微弱OPN蛋白表达,模型组肾小管-间质OPN与α-SMA蛋白表达明显高于对照组(p＜0.01),TGP 100,200mg·kg~(-1)给药组肾小管-间质OPN表达明显低于模型组(p＜0.01)。免疫组化显示对照组大鼠肾小管-间质有微弱α-SMA蛋白表达,模型组。肾小管-间质α-SMA蛋白表达明显高于对照组(p＜0.01),TGP 50,100,200mg·kg~(-1)给药组肾小管-间质α-SMA蛋白表达明显低于模型组(p＜0.01)。
结论糖尿病大鼠肾脏存在氧化应激反应,TGP抗糖尿病肾病的作用可能与其抗氧化活性有关。
Background and objective Diabetic nephropathy(DN) has become one of the main cause of end-stage renal disease(ESRD),but unfortunately the intimate mechanisms leading to the development and progression of renal injury are not yet fully known.The recent study in vivo and in vitro evidence demonstrated that oxidative stress play a major role in the development and progression of diabetic nephropathy,and that antioxidant treatment had significant protective effects on DN.Total glucosides of paeony(TGP) are active compounds extracted from the roots of the tradition herb Paeonia lactiflora Pall,its mainly composed of peoniflorin,hydroxide radical peoniflorin, peonin,albiflorin and benzoylpaeoniflorin.It possesses a variety of pharmacological functions,including anti-inflammation,anti-oxidative stress and immunoregulatory activity. The purpose of the present study was to investigate the effects of TGP on Oxidative stress in renal tissue of diabetic rats induced by STZ and explore the possible mechanism.
Methods Fifty adult male Sprague-Dawley rats were separated into five groups at random.Control group(n=10),model group(n=10),model group treated with TGP 50 mg·kg~(-1)(n=10),model group treated with TGP 100 mg·kg~(-1)(n=10) and model group treated with TGP 200 mg·kg~(-1)(n=10).To induce an experimental model of diabetes, rats received a single intraperitoneal injection of STZ(60mg·kg~(-1) d~(-1)).TGP was given by gavage.8 weeks after STZ injection,the following determinations were done in samples:(1) BG were determined according to standard methods;(2) Renal lesions were evaluated using PAS staining,the mean glomerular volume(V_G) and indices for tubulointerstitial injury(TII) were measured by using pathology image analysis system software;(3) Renal tissue T-AOC,GSH-PX,CAT,SOD were determined by spectrophotometric method;(4) Expression of nitrotyrosine(NT) was measured by Western blot analysis;(5) Expression of osteopontin(OPN) andα-smooth muscle actin (α-SMA) in renal tubulointerstitium were determined by immunohistochemistry method.
Results 1.BG,Body weight(BW) ratio of KW to BW(KW/BW):8 weeks after STZ injection,there was a significant increase in BG(P＜0.01) and significantly decreased in BW(p＜0.01) in diabetic rats compared with control group.The BG level of TGP group(50mg,100mg and200mg·kg~(-1)) have no statistically significant difference compared with model group.KW/BW in TGP group(50mg,100mg and 200mg·kg~(-1)) was decreased compared with model group,but there have no statistically significant.2. Renal pathologic morphology:Compared with control group,V_G and TII in model group was significantly increased.V_G in TGP group(50mg·kg~(-1)) was significantly lower than model group(P＜0.05),TII in TGP group(50mg·kg~(-1)) was lower than model group,but there have no statistically significant.V_G and TII in TGP group(100,200mg·kg~(-1)) was significantly lower than model group(P＜0.05,P＜0.01).3.T-AOC,
GSH-PX,CAT,SOD activities in renal tissue:The T-AOC,SOD and CAT activities in renal tissue of model group significantly decreased compared with that of control group(P＜0.01).TGP treatment with 200mg·kg~(-1) increased the T-AOC,SOD and CAT activities(P＜0.01,P＜0.05).In addition,GSH-PX have no difference between control group,model group,and TGP group(50,100,200mg·kg~(-1)).4.NT expression in renal tissue:Western blot analysis noted that the expression of NT protein in ranal tissue of model group increased by 3.4 folds to that of control group,TGP treatment with 50,100 and 200mg.kg~(-1) reduced the increased expression of NT protein by 41.2%,43.8%and 57.5%,respectively.5.OPN andα-SMA protein expression in renal tubulointerstitium:There was minimal immunohistohemistrical staining for OPN in renal tubulointerstitium of control group rats.Immunostaining for OPN was markedly increased in model group in tubulointerstitium(P＜0.01),elevated expression of OPN protein in renal tubulointerstitium in diabetic rats were only significantly inhibited by TGP treatment with 100 and 200mg.kg~(-1)(p＜0.01).There was minimal immunohistohemistrical staining forα-SMA in renal tubulointerstitium of control group rats.Immunostaining forα-SMA was markedly increased in model group in tubulointerstitium(P＜0.01),and increased expression ofα-SMA protein were significantly inhibited by TGP treatment with 50,100 and 200mg.kg~(-1)(p＜0.01).
Conclusion The oxidative stress is increased in the diabetic rat kidney,and TGP can prevent renal damage associated with diabetes by attenuating the oxidative stress.
引文
1.Xu S,Jiang B,Maitland KA,et al.The thromboxanereceptor antagonist S18886attenuates renal oxidant stress and proteinuria in diabetic apolipoprotein E-deficient mice.Diabetes,2006,55(1):110-119.
2.Beisswenger PJ,Drummond KS,Nelson RG,et al.Susceptibility to diabetic nephropathy is related to dicarbonyl and oxidative stress.Diabetes,2005,54(11):3274-3281.
3.Brownlee M.The pathobiology of diabetic complications:a unifying mechanism.Diabetes,2005,54(6):1615-1625.
4.Ceriello A,Mercuri F,Quagliaro L,et al.Detection of nitrotyrosine in the diabetic plasma:evidence of oxidative stress.Diabetologia,2001,44(7):834-838.
5.Wu LL,Chiou CC,Chang PY,et al.Urinary 8-OhdG:a marker of oxidative stress to DNA and arisk factor for cancer,atheroscleosis and diabetics.Clin Clim Acta,2004,339(1-2):1-9.
6.Nobecourt E,Jacqueminet S,Hansel B,et al.Defective antioxidative activity of small dense HDL3 particles in type 2 diabetes:relationship to elevated oxidative stress and hyperglycaemia.Diabetologia,2005,48(3):529-538.
7.高小荣,田庚元.白芍化学成分研究进展.中国新药杂志,2006,15(6):416-418.
8.徐叔云,陈敏珠,魏伟,等.免疫药理与临床.见:周金黄,刘干中主编.中药药理与临床研究进展(第一册),北京:中国科学技术出版社,1992:49-59.
9.Zheng YQ,Wei W.Total glucosides of paeony suppresses adjuvant arthritis in rats and intervenes cytokine-signaling between different types of synoviocytes.Int Immunopharmacol,2005,5(10):1560-1573.
10.刘玮,吴华璞,祝晓光,等.白芍总苷对全脑缺血再灌注损伤的保护作用.中国药理学通报,2004,20(2):211-214.
11.王晓明,李付彪,吕文伟,等.白芍总苷对犬急性心肌缺血的保护作用.吉林大学学报,2006,32(3):393-399.
12.孙敏,樊宏伟,赖红容,等.中药对高糖作用下牛肾小球系膜细胞增殖的影响.中国中医药信息杂志,2004,11(5):399-400.
13.Onozato ML,Tojo A,Goto A,et al.Oxidative stress and nitric oxide synthase in rat diabetic nephropathy:effects of ACEI and ARB.Kidney Int,2002,61(1):186-194.
14.Gilbert RE,Cooper ME.The tubulointerstitium in progressive diabetic kidney disease:More than an aftermath of glomerular injury? Kidney Int,1999,56(5):1627-37.
15.Nangaku Mo Mechanisms of tubulointerstitial injury in the kidney:final common pathways to end-stage renal failure.Intern Med,2004,43(1):9-17.
16.Liu K,Paterson AJ,Chin E,et al.Glucose stimulates protein modification by O-linked GlcNAc in pancreatic beta cells:linkage of O-linked GlcNAc to beta cell death.PNAS,2000,97(6):2820.
17.Parving HH,Lewis JB,Ravid M,et al.Prevalence and risk factors for microalbuminuria in a referred cohort of type Ⅱ diabetic patients:a global perspective.Kidney Int,2006,69(11):2057-2063.
18.Wu AY,Kong NC,de Leon FA,et al.An alarmingly high prevalence of diabetic nephropathy in Asian type 2 diabetic patients:the MicroAlbuminuria Prevalence (MAP) Study.Diabetologia,2005,48(1):17-26.
19.Schrijvers BF,De Vriese AS,Flyvbjerg A.From hyperglycemia to diabetic kidney disease:the role of metabolic,hemodynamic,intracellular factors and growth factors/cytokines.Endocr Rev,2004,25(6):971-1010.
20.Ha H,Yu MR,Choi YJ,et al.Role of high glocose-induced nuclear factor-kappaB activation in monocyte chemoattractant protein-1 expression by mesangial cells.J Am Soc Nephrol,2002,1 3(4):894-902.
21. Chavakis T, Bierhaus A, Al-Fakhri N, et al.The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J Exp Med, 2003,198(10): 1507-1515.
22. Weigert C, Brodbeck K, Sawadogo M, et al.Upstream stimulatory factor (USF) proteins induce human TGF-betal gene activation via the glucose-response element-1013/-1002 in mesangial cells: up-regulation of USF activity by the hexosamine biosynthetic pathway. J Biol Chem,2004,279(16):15908-15915.
23. Akahori H , Ota T , Torita M , et al. Tranilast prevents the progression of experimental diabetic nephropathythrough suppression of enhanced extracellular matrix gene expression. Journal of Pharmacology and Experimental Theraperimental Therapeutics, 2005,314(2): 514.
24. Wolf G, Reinking R, Zahner G, et al. Erk 1,2 phosphorylates p27(Kipl): Functional evidence for a role in high glucose-induced hypertrophy of mesangial cells. Diabetologia, 2003,46(8): 1090-1099.
25. Kedziora-Kornatowska K, Szram S, Kornatowski T, et al. Effect of vitamin E and vitamin C supplementation of antioxidative state and renal glomerular basement membrane thickness in diabetic kidney. Exp Nephrol, 2003, 95(4): el34-143.
26. Bhatti, Mankhey RW, Asico L, et al. Mechanisms of antioxidant and pro-oxidant effects of alpha-lopoic acid in the diabetic and nondiabetic kidney. Kidney Int, 2005,67(4): 1371-1380.
27. Naito Y , Uchiyama K, Aoi W, et al. Prevention of diabetic nephropathy by treatment with astaxanthin in diabetic db/db mice. Biofactors,2004,20(1):49-59.
28. Utimura R, Fujihara C, Clarice KF, et al. Mycophenolate mofetil prevents the development of glomerular injury in experimental diabetes. Kidney Int, 2003, 63(1): 209-216.
29. Chow F, Ozols E, David J, et al. Macrophage in mouse type 2 diabetic nephropathy: Correlation with diabetic state and progressive renal injury. Kidney Int, 2004,65(1): 116-128.
30. Wu YG, Lin H, Qi XM, et al. Prevention of early renal injury by mycophenolate mofetil and its mechanism in experimental diabetes. Int Immunopharmaco, 2006, 6(3): 445-53.
31. Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supple-mentation and cardiovascular events in high-risk patients.The Heart Outcomes Prevention Evaluation Study Investi-gators. N Engl Med, 2003, 342(3): 154-160.
32. Boaz M, Smetana S, Weinstein T, et al. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet, 2000, 356(9237): 1213-1218.
33. Sacco M, Pellegrini F, Roncaglioni MC, et al. Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial. Diabetes Care, 2003, 26(12): 3264-3272.
34. Opara EC. Oxidative stress , micronutrients , diabetes mellitusand its complications. J R Soc Health, 2002,122(1): 28-34.
35. Evans JL, Goldfine ID, Madux BA, et al. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev, 2002, 23(5): 599-622.
36. Mason RP, Walter MF, Jacob RF, et al. Effects of HMG-CoA reductase inhibitors on endothelial function: role of microdomains and oxidative stress. Circulation, 2004, 109(21 Suppl 1): 1134-41.
37. Jones SP, Teshima Y, Akao M, et al. Simvastatin attenuates oxidant-induced mitochondrial dysfunction in cardiac myocytes. Circ Res, 2003, 93(8): 697-699.
38. Bagi Z, Koller A, Kaley G. PPARgamma activation, by reducing oxidative stress, increases NO bioavailability in coronary arterioles of mice with Type 2 diabetes. Am J Physiol Heart Circ Physiol, 2004, 286(2): 742-748.
39.Reddi AS,Bollineni JS.Selenium-deficient diet induces renal oxidative stress and injury via TGF-betal in normal and diabetic rats.Kidney Int,2001,59(4):1342-1353.
40.Takagi K,Harada M.Pharmacological studies on herb paeony root.I.Central effects of paeoniflorin and combined effects with licorice component Fm 100.Yakugaku Zasshi,1969,89(7):879-886.
41.Takagi K,Harada M.Pharmacological studies on herb paeony root.Ⅱ.anti-inflammatory effect,inhibitory effect on gastric juice secretion,preventive effect on stress ulcer,antidiuretic effect of paeoniflorin and combined effects with licorice component Fm 100.Yakugaku Zasshi,1969,89(7):887-892.
42.Takagi K,Harada M.Pharmacological studies on herb paeony root.3.Effects of paeoniflorin on circulatory and respiratory systems and isolated organs.Yakugaku Zasshi,1969,89(7):893-898.
43.高崇凯,吴雁,王勇,等.白芍总苷粉针剂的抗炎镇痛作用.中国新药药理与临床药理,2002,13(3):163-165.
44.高本波,戴利明,徐叔云.丹皮总甙和白芍总甙对自由基的清除作用的影响.维坊医学院学报,1996,18(1):43-46.
45.Wang H,Wei W,Wang NP,et al.Effects of total glucosides of peony on immunological hepatic fibrosis in rats.World J Gastroenterol,2005,11(14):2124-2129.
46.陈敏珠,叙叔云.白芍总甙的免疫调节与抗炎作用.见:周金黄,李小玉,荣康泰主编.免疫药理学进展:基础与临床.北京:中国科学技术出版社,1993,133-51.
47.周玲玲,魏伟,沈玉先,等.白芍总苷对小鼠系统性红斑狼疮样改变的保护作用.中国药理学通报,2002,18(2):175-177.
48.王永祥,陈敏珠,徐叔云.白芍总苷的镇痛作用.中国药理学与毒理学杂志,1988,2(1):6-9.
49.戴俐明,陈学广,徐叔云.白芍总甙对实验性肝炎的保护作用.中国药理学通报,993,9(6):449-453.
50.石鹏.白芍总苷对大鼠主动型Heymann肾炎的作用.第四军医大学学报,2005,26(18):1661-1663.
51.黄黎明,石鹏,王喜习.白芍提取物对IgA肾炎小鼠的治疗作用.中药学,2003,26(2):109-111.
52.Yang HO,Ko WK,Kim JY,et al.Paeoniflorin:an antihyperlipidemic agent from Paeonia lactiflora.Fitoterapia,2004,75(1):45-49.
53.Nishikawa T,Edelstein D,Du XX,et al.Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage.Nature,2000,404(6779):787-790.
54.Kang SW,Natarajan R,Shahed A,et al.Role of 12-1ipoxygenase in the stimulation of p38 mitogen-aetivated protein kinase and collagen alpha 5(Ⅳ) in experimental diabetic nephropathy and in glcose stimulated podocytes.J Am Soc Nephrol,2003,14(12):3178-3187.
55.Wang P,Zweier JL.Measurement of nitric oxide and peroxynitrite generation in the postischemic heart.J Biol Chem,1996,271(46):29223 -29230.
56.Raij L,Baylis C.Glomerular actions of nitric oxide.Kidney Int,1995,48(1):20-32.
57.Escames G,Leon J,Macias M,et al.Melatonin counteracts lipopolysaccharide-induced expression and activity of mitochondrial nitric oxide synthase in rats.FASEB J,2003,17(8):932-934.
58.Chow FY,Nikolic-Paterson DJ,Atkins RC,et al.Macrophages in streptozotocin-induced diabetic nephropathy:potential role in the renal fibrosis.Nephrol Dial Transplant,2004;19(12):2987-2996.
59.Panzer U,Thaiss F,Zahner G,et al.Monocyte chemoattractant protein-1 and osteopontin differentially regulate monocytes recruitment in experimental glomerulonephritis. Kidney Int, 2001; 59(5): 1762-1769.
60. Giachelli CM, Lombardi D, Johnson RJ, et al. Evidence for a role of osteopontin in macrophage infiltration in response to pathological stimuli in vivo. Am J Pathol, 1998; 152(2): 353-358.
61. Persy VP, Verhulst A, Ysebaert DK, et al. Reduced postischemic macrophage infiltration and interstitial fibrosis in osteopontin knockout mice. Kidney Int, 2003, 63(2): 543-553.
62. Fan JM, Ng YY, Hill PA, et al. Transforming growth factor-beta regulates epithelial-myofibroblast transdifferentiation in vitro. Kidney Int, 1999, 56(4): 1455-1467.
1.Brownlee M.The pathobiology of diabetic complications:a unifying mechanism.Diabetes,2005,54(6):1615-1625.
2.刘志明,孙亮亮.氧化应激在糖尿病发病机制中作用的认识.内科理论与实践,2007,2(3):153-156.
3.Ceriello A,Mercuri F,Quagliaro L,et al.Detection of nitrotyrosine in the diabetic plasma:evidence of oxidative stress.Diabetologia,2001,44(7):834-838.
4.Wu LL,Chiou CC,Chang PY,et al.Urinary 8-OhdG:a marker of oxidative stress to DNA and arisk factor for cancer,atheroscleosis and diabetics.Clin Clim Acta,2004,339(1-2):1-9.
5.Nobecourt E,Jacqueminet S,Hansel B,et al.Defective antioxidative activity of small dense HDL3 particles in type 2 diabetes:relationship to elevated oxidative stress and hyperglycaemia.Diabetologia,2005,48(3):529-538.
6.Nishikawa T,Edelstein D,Du XX,et al.Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage.Nature,2000,404(6779):787-790.
7.Brownlee M.Biochemistry and molecular cell biology of diabetic complications.Nature,2001,414(6865):813-820.
8.Kang SW,Natarajan R,Shahed A,et al.Role of 12-lipoxygenase in the stimulation of p38 mitogen-activated protein kinase and collagen alpha5(Ⅳ) in experimental diabetic nephropathy and in glcose stimulated podocytes.J Am Soc Nephrol,2003,14(12):3 178-3187.
9.Ha H,Yu MR,Choi YJ,et al.Role of high glocose-induced nuclear factor-kappaB activation in monocyte chemoattractant protein-1 expression by mesangial cells.J Am Soc Nephrol,2002,13(4):894-902.
10. Chavakis T, Bierhaus A, Al-Fakhri N, et al. The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J Exp Med, 2003,198(10): 1507-1515.
11. Fukami K, Ueda S, Yamagishi S, et al. AGEs activate mesangial TGF-beta-Smad signaling via an angiotensin II type I receptor interaction. Kidney Int, 2004, 66(6): 2137-2147.
12. Weigert C, Brodbeck K, Sawadogo M, et al. Upstream stimulatory factor (USF) proteins induce human TGF-betal gene activation via the glucose-response element-1013/-1002 in mesangial cells: up-regulation of USF activity by the hexosamine biosynthetic pathway. J Biol Chem, 2004,279(16): 15908-15915.
13. Akahori H , Ota T , Torita M ,et al. Tranilast prevents the progression of experimental diabetic nephropathythrough suppression of enhanced extracellular matrix gene expression. Journal of Pharmacology and Experimental Theraperimental Therapeutics, 2005,314(2): 514.
14. Wolf G, Reinking R, Zahner G, et al. Erk 1,2 phosphorylates p27(Kipl): Functional evidence for a role in high glucose-induced hypertrophy of mesangial cells. Diabetologia, 2003,46(8): 1090-1099.
15. Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supple-mentation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investi-gators. N Engl Med, 2003, 342(3): 154-160.
16. Boaz M, Smetana S, Weinstein T, et al. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet, 2000, 356(9237): 1213-1218.
17. Sacco M, Pellegrini F, Roncaglioni MC, et al. Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial. Diabetes Care, 2003, 26(12): 3264-3272.
18. Fang YZ, Yang S , Wu G. Free radicals , antioxidants , and nutrition. Nutrition, 2002,18(10): 872-879.
19. Opara EC. Oxidative stress , micronutrients , diabetes mellitusand its complications. J R Soc Health, 2002,122(1): 28-34.
20. Evans JL, Goldfine ID, Madux BA, et al. Oxidative stress and stress-activated signaling pathways :a unifying hypothesis of type 2 diabetes. Endocr Rev, 2002, 23(5): 599-622.
21. Maritim AC, Sanders RA, Watkins JB 3rd. Effects of al2 pha21ipoic acid on biomarkers of oxidative stress in streptozotocin-induced diabetic rats. J Nutr Biochem, 2003, 14(5): 288-294.
22. Evans JL, Goldfine ID, Madux BA, et al. Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction ? Diabetes, 2003, 52(1): 1-8.
23. Stadler K, Jenei V, von Bolcshazy G, et al. Role of free radicals and reactive nitrogen species in the late complications of diabetes mellitus in rats. Orv Hetil, 2004,145(21): 1135-1140.
24. Feldman EL. Oxidative stress and diabetic neuropathy : a new understanding of an old problem. J Clin Invest, 2003, 111(4): 431-433.
25. Baydas G, Canatan H, Turkoglu A. Comparative analysis of the protective effects of melatonin and vitamin E on streptozocin-induced diabetes mellitus. J Pineal Res, 2002, 32(4): 225-230.
26. Aksoy N, Vural H, Sabuncu T, et al. Effects of melatonin on oxidative-antioxidative status of tissues in streptozotocin-induced diabetic rats. Cell Biochem Funct, 2003, 21(2): 121-125.
27. Anwar MM, Meki MA. Oxidative stress in streptozotocin-induced diabetic rats : effects of garlic oil and melatonin. Comp Biochem Physiol, 2003, 135(4): 539-547.
28. Higashi Y, Yoshizumi M. Endothelial function. Nippon Rinsho, 2003, 61(7): 1138-1144.
29. Jandeleit-Dahm K, Cao Z, Cox AJ, et al. Role of hyperlipidemia in progressive renal disease: focus on diabetic nephropathy. Kidney Int Suppl, 1999, 7: S31-36.
30. Mason RP, Walter MF, Jacob RF, et al. Effects of HMG-CoA reductase inhibitors on endothelial function: role of microdomains and oxidative stress. Circulation, 2004,109(21 Suppl 1): 1134-41.
31. Jones SP, Teshima Y, Akao M, et al. Simvastatin attenuates oxidant-induced mitochondrial dysfunction in cardiac myocytes. Circ Res, 2003, 93(8): 697-699.
32. Deakin S, Leviev I, Guernier S, et al. Simvastatin modulates expression of the PON1 gene and increases serum paraoxonase: a role for sterol regulatory element-binding protein-2. Arterioscler Thromb Vasc Biol, 2003, 23(11): 2083-2089.
33. Endo K, Miyashita Y, Sasaki H, et al. Probucol and atorvastatin decrease urinary 8-hydroxy-2'-deoxyguanosine in patients with diabetes and hypercholesterolemia. J Athemscler Thmmb, 2006,13(1): 68-75.
34. Crosby MB, Svenson J, Gilkeson GS, et al. A novel PPAR response element in the murine iNOS promoter. Mol Immunol, 2005,42(11): 1303-1310.
35. Bagi Z, Koller A, Kaley G. PPARgamma activation,by reducing oxidative stress,increases NO bioavailability in coronary arterioles of mice with Type 2 diabetes. Am J Physiol Heart Circ Physiol, 2004, 286(2): 742-748.
36. Reddi AS, Bollineni JS. Selenium-deficient diet induces renal oxidative stress and injury via TGF-betal in normal and diabetic rats. Kidney Int, 2001, 59(4): 1342-1353.
37. Xu S Y, Chen MZ, Wei W, et al. Immunopharmacology and clinic. In: Zhou JH, Liu GZ, editor. Progress in pharmacology and clinics of Chinese Materia Medica Research, 1st. Bei Jing: Science and Technology of China Press, 1992: 49-59.
38.Zheng YQ,Wei W.Total glucosides of paeony suppresses adjuvant arthritis in rats and intervenes cytokine-signaling between different types of synoviocytes.Int Immunopharmacol,2005,5(10):1560-1573.
39.Wang H,Wei W,Wang NP,et al.Effects of total glucosides of peony on immunological hepatic fibrosis in rats.World J Gastroenterol,2005;11(14):2124-2129.
40.周玲玲,魏伟,沈玉先,等.白芍总苷对小鼠系统性红斑狼疮样改变的保护作用.中国药理学通报,2002,18(2):175-177.
41.黄黎明,石鹏,王喜习.白芍提取物对IgA肾炎小鼠的治疗作用.中药材,2003;26(2):109-110.
42.刘玮,吴华璞,祝晓光,明亮.白芍总苷对全脑缺血再灌注损伤的保护作用.中国药理学通报,2004,20(2):211-214.
43.王晓明,李付彪,吕文伟,陈霞.白芍总苷对犬急性心肌缺血的保护作用.吉林大学学报,2006,32(3):393-399.
44.高本波,戴利明,徐叔云.丹皮总甙和白芍总甙对自由基的清除作用的影响.维坊医学院学报,1996,18(1):43-46.
2.Beisswenger PJ,Drummond KS,Nelson RG,et al.Susceptibility to diabetic nephropathy is related to dicarbonyl and oxidative stress.Diabetes,2005,54(11):3274-3281.
3.Brownlee M.The pathobiology of diabetic complications:a unifying mechanism.Diabetes,2005,54(6):1615-1625.
4.Ceriello A,Mercuri F,Quagliaro L,et al.Detection of nitrotyrosine in the diabetic plasma:evidence of oxidative stress.Diabetologia,2001,44(7):834-838.
5.Wu LL,Chiou CC,Chang PY,et al.Urinary 8-OhdG:a marker of oxidative stress to DNA and arisk factor for cancer,atheroscleosis and diabetics.Clin Clim Acta,2004,339(1-2):1-9.
6.Nobecourt E,Jacqueminet S,Hansel B,et al.Defective antioxidative activity of small dense HDL3 particles in type 2 diabetes:relationship to elevated oxidative stress and hyperglycaemia.Diabetologia,2005,48(3):529-538.
7.高小荣,田庚元.白芍化学成分研究进展.中国新药杂志,2006,15(6):416-418.
8.徐叔云,陈敏珠,魏伟,等.免疫药理与临床.见:周金黄,刘干中主编.中药药理与临床研究进展(第一册),北京:中国科学技术出版社,1992:49-59.
9.Zheng YQ,Wei W.Total glucosides of paeony suppresses adjuvant arthritis in rats and intervenes cytokine-signaling between different types of synoviocytes.Int Immunopharmacol,2005,5(10):1560-1573.
10.刘玮,吴华璞,祝晓光,等.白芍总苷对全脑缺血再灌注损伤的保护作用.中国药理学通报,2004,20(2):211-214.
11.王晓明,李付彪,吕文伟,等.白芍总苷对犬急性心肌缺血的保护作用.吉林大学学报,2006,32(3):393-399.
12.孙敏,樊宏伟,赖红容,等.中药对高糖作用下牛肾小球系膜细胞增殖的影响.中国中医药信息杂志,2004,11(5):399-400.
13.Onozato ML,Tojo A,Goto A,et al.Oxidative stress and nitric oxide synthase in rat diabetic nephropathy:effects of ACEI and ARB.Kidney Int,2002,61(1):186-194.
14.Gilbert RE,Cooper ME.The tubulointerstitium in progressive diabetic kidney disease:More than an aftermath of glomerular injury? Kidney Int,1999,56(5):1627-37.
15.Nangaku Mo Mechanisms of tubulointerstitial injury in the kidney:final common pathways to end-stage renal failure.Intern Med,2004,43(1):9-17.
16.Liu K,Paterson AJ,Chin E,et al.Glucose stimulates protein modification by O-linked GlcNAc in pancreatic beta cells:linkage of O-linked GlcNAc to beta cell death.PNAS,2000,97(6):2820.
17.Parving HH,Lewis JB,Ravid M,et al.Prevalence and risk factors for microalbuminuria in a referred cohort of type Ⅱ diabetic patients:a global perspective.Kidney Int,2006,69(11):2057-2063.
18.Wu AY,Kong NC,de Leon FA,et al.An alarmingly high prevalence of diabetic nephropathy in Asian type 2 diabetic patients:the MicroAlbuminuria Prevalence (MAP) Study.Diabetologia,2005,48(1):17-26.
19.Schrijvers BF,De Vriese AS,Flyvbjerg A.From hyperglycemia to diabetic kidney disease:the role of metabolic,hemodynamic,intracellular factors and growth factors/cytokines.Endocr Rev,2004,25(6):971-1010.
20.Ha H,Yu MR,Choi YJ,et al.Role of high glocose-induced nuclear factor-kappaB activation in monocyte chemoattractant protein-1 expression by mesangial cells.J Am Soc Nephrol,2002,1 3(4):894-902.
21. Chavakis T, Bierhaus A, Al-Fakhri N, et al.The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J Exp Med, 2003,198(10): 1507-1515.
22. Weigert C, Brodbeck K, Sawadogo M, et al.Upstream stimulatory factor (USF) proteins induce human TGF-betal gene activation via the glucose-response element-1013/-1002 in mesangial cells: up-regulation of USF activity by the hexosamine biosynthetic pathway. J Biol Chem,2004,279(16):15908-15915.
23. Akahori H , Ota T , Torita M , et al. Tranilast prevents the progression of experimental diabetic nephropathythrough suppression of enhanced extracellular matrix gene expression. Journal of Pharmacology and Experimental Theraperimental Therapeutics, 2005,314(2): 514.
24. Wolf G, Reinking R, Zahner G, et al. Erk 1,2 phosphorylates p27(Kipl): Functional evidence for a role in high glucose-induced hypertrophy of mesangial cells. Diabetologia, 2003,46(8): 1090-1099.
25. Kedziora-Kornatowska K, Szram S, Kornatowski T, et al. Effect of vitamin E and vitamin C supplementation of antioxidative state and renal glomerular basement membrane thickness in diabetic kidney. Exp Nephrol, 2003, 95(4): el34-143.
26. Bhatti, Mankhey RW, Asico L, et al. Mechanisms of antioxidant and pro-oxidant effects of alpha-lopoic acid in the diabetic and nondiabetic kidney. Kidney Int, 2005,67(4): 1371-1380.
27. Naito Y , Uchiyama K, Aoi W, et al. Prevention of diabetic nephropathy by treatment with astaxanthin in diabetic db/db mice. Biofactors,2004,20(1):49-59.
28. Utimura R, Fujihara C, Clarice KF, et al. Mycophenolate mofetil prevents the development of glomerular injury in experimental diabetes. Kidney Int, 2003, 63(1): 209-216.
29. Chow F, Ozols E, David J, et al. Macrophage in mouse type 2 diabetic nephropathy: Correlation with diabetic state and progressive renal injury. Kidney Int, 2004,65(1): 116-128.
30. Wu YG, Lin H, Qi XM, et al. Prevention of early renal injury by mycophenolate mofetil and its mechanism in experimental diabetes. Int Immunopharmaco, 2006, 6(3): 445-53.
31. Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supple-mentation and cardiovascular events in high-risk patients.The Heart Outcomes Prevention Evaluation Study Investi-gators. N Engl Med, 2003, 342(3): 154-160.
32. Boaz M, Smetana S, Weinstein T, et al. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet, 2000, 356(9237): 1213-1218.
33. Sacco M, Pellegrini F, Roncaglioni MC, et al. Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial. Diabetes Care, 2003, 26(12): 3264-3272.
34. Opara EC. Oxidative stress , micronutrients , diabetes mellitusand its complications. J R Soc Health, 2002,122(1): 28-34.
35. Evans JL, Goldfine ID, Madux BA, et al. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev, 2002, 23(5): 599-622.
36. Mason RP, Walter MF, Jacob RF, et al. Effects of HMG-CoA reductase inhibitors on endothelial function: role of microdomains and oxidative stress. Circulation, 2004, 109(21 Suppl 1): 1134-41.
37. Jones SP, Teshima Y, Akao M, et al. Simvastatin attenuates oxidant-induced mitochondrial dysfunction in cardiac myocytes. Circ Res, 2003, 93(8): 697-699.
38. Bagi Z, Koller A, Kaley G. PPARgamma activation, by reducing oxidative stress, increases NO bioavailability in coronary arterioles of mice with Type 2 diabetes. Am J Physiol Heart Circ Physiol, 2004, 286(2): 742-748.
39.Reddi AS,Bollineni JS.Selenium-deficient diet induces renal oxidative stress and injury via TGF-betal in normal and diabetic rats.Kidney Int,2001,59(4):1342-1353.
40.Takagi K,Harada M.Pharmacological studies on herb paeony root.I.Central effects of paeoniflorin and combined effects with licorice component Fm 100.Yakugaku Zasshi,1969,89(7):879-886.
41.Takagi K,Harada M.Pharmacological studies on herb paeony root.Ⅱ.anti-inflammatory effect,inhibitory effect on gastric juice secretion,preventive effect on stress ulcer,antidiuretic effect of paeoniflorin and combined effects with licorice component Fm 100.Yakugaku Zasshi,1969,89(7):887-892.
42.Takagi K,Harada M.Pharmacological studies on herb paeony root.3.Effects of paeoniflorin on circulatory and respiratory systems and isolated organs.Yakugaku Zasshi,1969,89(7):893-898.
43.高崇凯,吴雁,王勇,等.白芍总苷粉针剂的抗炎镇痛作用.中国新药药理与临床药理,2002,13(3):163-165.
44.高本波,戴利明,徐叔云.丹皮总甙和白芍总甙对自由基的清除作用的影响.维坊医学院学报,1996,18(1):43-46.
45.Wang H,Wei W,Wang NP,et al.Effects of total glucosides of peony on immunological hepatic fibrosis in rats.World J Gastroenterol,2005,11(14):2124-2129.
46.陈敏珠,叙叔云.白芍总甙的免疫调节与抗炎作用.见:周金黄,李小玉,荣康泰主编.免疫药理学进展:基础与临床.北京:中国科学技术出版社,1993,133-51.
47.周玲玲,魏伟,沈玉先,等.白芍总苷对小鼠系统性红斑狼疮样改变的保护作用.中国药理学通报,2002,18(2):175-177.
48.王永祥,陈敏珠,徐叔云.白芍总苷的镇痛作用.中国药理学与毒理学杂志,1988,2(1):6-9.
49.戴俐明,陈学广,徐叔云.白芍总甙对实验性肝炎的保护作用.中国药理学通报,993,9(6):449-453.
50.石鹏.白芍总苷对大鼠主动型Heymann肾炎的作用.第四军医大学学报,2005,26(18):1661-1663.
51.黄黎明,石鹏,王喜习.白芍提取物对IgA肾炎小鼠的治疗作用.中药学,2003,26(2):109-111.
52.Yang HO,Ko WK,Kim JY,et al.Paeoniflorin:an antihyperlipidemic agent from Paeonia lactiflora.Fitoterapia,2004,75(1):45-49.
53.Nishikawa T,Edelstein D,Du XX,et al.Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage.Nature,2000,404(6779):787-790.
54.Kang SW,Natarajan R,Shahed A,et al.Role of 12-1ipoxygenase in the stimulation of p38 mitogen-aetivated protein kinase and collagen alpha 5(Ⅳ) in experimental diabetic nephropathy and in glcose stimulated podocytes.J Am Soc Nephrol,2003,14(12):3178-3187.
55.Wang P,Zweier JL.Measurement of nitric oxide and peroxynitrite generation in the postischemic heart.J Biol Chem,1996,271(46):29223 -29230.
56.Raij L,Baylis C.Glomerular actions of nitric oxide.Kidney Int,1995,48(1):20-32.
57.Escames G,Leon J,Macias M,et al.Melatonin counteracts lipopolysaccharide-induced expression and activity of mitochondrial nitric oxide synthase in rats.FASEB J,2003,17(8):932-934.
58.Chow FY,Nikolic-Paterson DJ,Atkins RC,et al.Macrophages in streptozotocin-induced diabetic nephropathy:potential role in the renal fibrosis.Nephrol Dial Transplant,2004;19(12):2987-2996.
59.Panzer U,Thaiss F,Zahner G,et al.Monocyte chemoattractant protein-1 and osteopontin differentially regulate monocytes recruitment in experimental glomerulonephritis. Kidney Int, 2001; 59(5): 1762-1769.
60. Giachelli CM, Lombardi D, Johnson RJ, et al. Evidence for a role of osteopontin in macrophage infiltration in response to pathological stimuli in vivo. Am J Pathol, 1998; 152(2): 353-358.
61. Persy VP, Verhulst A, Ysebaert DK, et al. Reduced postischemic macrophage infiltration and interstitial fibrosis in osteopontin knockout mice. Kidney Int, 2003, 63(2): 543-553.
62. Fan JM, Ng YY, Hill PA, et al. Transforming growth factor-beta regulates epithelial-myofibroblast transdifferentiation in vitro. Kidney Int, 1999, 56(4): 1455-1467.
1.Brownlee M.The pathobiology of diabetic complications:a unifying mechanism.Diabetes,2005,54(6):1615-1625.
2.刘志明,孙亮亮.氧化应激在糖尿病发病机制中作用的认识.内科理论与实践,2007,2(3):153-156.
3.Ceriello A,Mercuri F,Quagliaro L,et al.Detection of nitrotyrosine in the diabetic plasma:evidence of oxidative stress.Diabetologia,2001,44(7):834-838.
4.Wu LL,Chiou CC,Chang PY,et al.Urinary 8-OhdG:a marker of oxidative stress to DNA and arisk factor for cancer,atheroscleosis and diabetics.Clin Clim Acta,2004,339(1-2):1-9.
5.Nobecourt E,Jacqueminet S,Hansel B,et al.Defective antioxidative activity of small dense HDL3 particles in type 2 diabetes:relationship to elevated oxidative stress and hyperglycaemia.Diabetologia,2005,48(3):529-538.
6.Nishikawa T,Edelstein D,Du XX,et al.Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage.Nature,2000,404(6779):787-790.
7.Brownlee M.Biochemistry and molecular cell biology of diabetic complications.Nature,2001,414(6865):813-820.
8.Kang SW,Natarajan R,Shahed A,et al.Role of 12-lipoxygenase in the stimulation of p38 mitogen-activated protein kinase and collagen alpha5(Ⅳ) in experimental diabetic nephropathy and in glcose stimulated podocytes.J Am Soc Nephrol,2003,14(12):3 178-3187.
9.Ha H,Yu MR,Choi YJ,et al.Role of high glocose-induced nuclear factor-kappaB activation in monocyte chemoattractant protein-1 expression by mesangial cells.J Am Soc Nephrol,2002,13(4):894-902.
10. Chavakis T, Bierhaus A, Al-Fakhri N, et al. The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J Exp Med, 2003,198(10): 1507-1515.
11. Fukami K, Ueda S, Yamagishi S, et al. AGEs activate mesangial TGF-beta-Smad signaling via an angiotensin II type I receptor interaction. Kidney Int, 2004, 66(6): 2137-2147.
12. Weigert C, Brodbeck K, Sawadogo M, et al. Upstream stimulatory factor (USF) proteins induce human TGF-betal gene activation via the glucose-response element-1013/-1002 in mesangial cells: up-regulation of USF activity by the hexosamine biosynthetic pathway. J Biol Chem, 2004,279(16): 15908-15915.
13. Akahori H , Ota T , Torita M ,et al. Tranilast prevents the progression of experimental diabetic nephropathythrough suppression of enhanced extracellular matrix gene expression. Journal of Pharmacology and Experimental Theraperimental Therapeutics, 2005,314(2): 514.
14. Wolf G, Reinking R, Zahner G, et al. Erk 1,2 phosphorylates p27(Kipl): Functional evidence for a role in high glucose-induced hypertrophy of mesangial cells. Diabetologia, 2003,46(8): 1090-1099.
15. Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supple-mentation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investi-gators. N Engl Med, 2003, 342(3): 154-160.
16. Boaz M, Smetana S, Weinstein T, et al. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet, 2000, 356(9237): 1213-1218.
17. Sacco M, Pellegrini F, Roncaglioni MC, et al. Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial. Diabetes Care, 2003, 26(12): 3264-3272.
18. Fang YZ, Yang S , Wu G. Free radicals , antioxidants , and nutrition. Nutrition, 2002,18(10): 872-879.
19. Opara EC. Oxidative stress , micronutrients , diabetes mellitusand its complications. J R Soc Health, 2002,122(1): 28-34.
20. Evans JL, Goldfine ID, Madux BA, et al. Oxidative stress and stress-activated signaling pathways :a unifying hypothesis of type 2 diabetes. Endocr Rev, 2002, 23(5): 599-622.
21. Maritim AC, Sanders RA, Watkins JB 3rd. Effects of al2 pha21ipoic acid on biomarkers of oxidative stress in streptozotocin-induced diabetic rats. J Nutr Biochem, 2003, 14(5): 288-294.
22. Evans JL, Goldfine ID, Madux BA, et al. Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction ? Diabetes, 2003, 52(1): 1-8.
23. Stadler K, Jenei V, von Bolcshazy G, et al. Role of free radicals and reactive nitrogen species in the late complications of diabetes mellitus in rats. Orv Hetil, 2004,145(21): 1135-1140.
24. Feldman EL. Oxidative stress and diabetic neuropathy : a new understanding of an old problem. J Clin Invest, 2003, 111(4): 431-433.
25. Baydas G, Canatan H, Turkoglu A. Comparative analysis of the protective effects of melatonin and vitamin E on streptozocin-induced diabetes mellitus. J Pineal Res, 2002, 32(4): 225-230.
26. Aksoy N, Vural H, Sabuncu T, et al. Effects of melatonin on oxidative-antioxidative status of tissues in streptozotocin-induced diabetic rats. Cell Biochem Funct, 2003, 21(2): 121-125.
27. Anwar MM, Meki MA. Oxidative stress in streptozotocin-induced diabetic rats : effects of garlic oil and melatonin. Comp Biochem Physiol, 2003, 135(4): 539-547.
28. Higashi Y, Yoshizumi M. Endothelial function. Nippon Rinsho, 2003, 61(7): 1138-1144.
29. Jandeleit-Dahm K, Cao Z, Cox AJ, et al. Role of hyperlipidemia in progressive renal disease: focus on diabetic nephropathy. Kidney Int Suppl, 1999, 7: S31-36.
30. Mason RP, Walter MF, Jacob RF, et al. Effects of HMG-CoA reductase inhibitors on endothelial function: role of microdomains and oxidative stress. Circulation, 2004,109(21 Suppl 1): 1134-41.
31. Jones SP, Teshima Y, Akao M, et al. Simvastatin attenuates oxidant-induced mitochondrial dysfunction in cardiac myocytes. Circ Res, 2003, 93(8): 697-699.
32. Deakin S, Leviev I, Guernier S, et al. Simvastatin modulates expression of the PON1 gene and increases serum paraoxonase: a role for sterol regulatory element-binding protein-2. Arterioscler Thromb Vasc Biol, 2003, 23(11): 2083-2089.
33. Endo K, Miyashita Y, Sasaki H, et al. Probucol and atorvastatin decrease urinary 8-hydroxy-2'-deoxyguanosine in patients with diabetes and hypercholesterolemia. J Athemscler Thmmb, 2006,13(1): 68-75.
34. Crosby MB, Svenson J, Gilkeson GS, et al. A novel PPAR response element in the murine iNOS promoter. Mol Immunol, 2005,42(11): 1303-1310.
35. Bagi Z, Koller A, Kaley G. PPARgamma activation,by reducing oxidative stress,increases NO bioavailability in coronary arterioles of mice with Type 2 diabetes. Am J Physiol Heart Circ Physiol, 2004, 286(2): 742-748.
36. Reddi AS, Bollineni JS. Selenium-deficient diet induces renal oxidative stress and injury via TGF-betal in normal and diabetic rats. Kidney Int, 2001, 59(4): 1342-1353.
37. Xu S Y, Chen MZ, Wei W, et al. Immunopharmacology and clinic. In: Zhou JH, Liu GZ, editor. Progress in pharmacology and clinics of Chinese Materia Medica Research, 1st. Bei Jing: Science and Technology of China Press, 1992: 49-59.
38.Zheng YQ,Wei W.Total glucosides of paeony suppresses adjuvant arthritis in rats and intervenes cytokine-signaling between different types of synoviocytes.Int Immunopharmacol,2005,5(10):1560-1573.
39.Wang H,Wei W,Wang NP,et al.Effects of total glucosides of peony on immunological hepatic fibrosis in rats.World J Gastroenterol,2005;11(14):2124-2129.
40.周玲玲,魏伟,沈玉先,等.白芍总苷对小鼠系统性红斑狼疮样改变的保护作用.中国药理学通报,2002,18(2):175-177.
41.黄黎明,石鹏,王喜习.白芍提取物对IgA肾炎小鼠的治疗作用.中药材,2003;26(2):109-110.
42.刘玮,吴华璞,祝晓光,明亮.白芍总苷对全脑缺血再灌注损伤的保护作用.中国药理学通报,2004,20(2):211-214.
43.王晓明,李付彪,吕文伟,陈霞.白芍总苷对犬急性心肌缺血的保护作用.吉林大学学报,2006,32(3):393-399.
44.高本波,戴利明,徐叔云.丹皮总甙和白芍总甙对自由基的清除作用的影响.维坊医学院学报,1996,18(1):43-46.