补气活血化痰汤抗动脉粥样硬化的实验研究
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摘要
目的
通过动物实验观察补气活血化痰汤抗兔动脉粥样硬化斑块形成的作用及其对血浆内皮素—1(ET—1)和一氧化氮(NO)及血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL—C)、低密度脂蛋白胆固醇(LDL—C)、载脂蛋白A—1(ApoA—1)、载脂蛋白B(ApoB)水平的影响。
方法
采用免疫损伤加高胆固醇饮食方法建立新西兰大耳兔动脉粥样硬化模型，设立硝苯吡啶对照，观察补气活血化痰汤对动脉粥样硬化模型兔主动脉、冠状动脉粥样硬化病变及血脂、血浆NO、ET—1水平的影响。光镜下观察模型兔主动脉、冠状动脉的病变程度，酶法测定血脂、血浆NO水平，放射免疫法测定血浆ET—1含量。
结果
1．免疫损伤合并高胆固醇喂饲可诱发模型兔主动脉AS病变产生。
2．补气活血化痰汤能使模型兔主动脉AS病变减轻(P＜0.05)。
3．补气活血化痰汤能使ApoA—1、HDL—C、NO水平上升(P＜0.05、P＜0.01)，能使LDL—C、TC、ApoB、ET-1水平下降(P＜0.05、P＜0.01)。
结论
中药补气活血化痰汤具有较好的抗动脉粥样硬化作用，这可能与其能够有效地调节NO／ET-1平衡失调及血脂水平有关。
Objective:
To investigate the antiatherogenetic activity of Chinese medicine Buqihuoxuehuatan decoction in male rabbit fed an atherogenic diet and the effect of the total cholesterol, triglycerides, low-density lipoprotein-cholesterol apolipoprotein B high- density lipoprotein- cholesterol and apolipoprotein Al level in serum, and investigate the nitric oxide and endothlin-1 level in plasma.
Materials and Methods:
An atherosclerotic rabbit model was established by feeding high cholesterol diet supplemented by bovine serum albumin injection bolus. The rabbits were randomly divided into three groups: the model group, Buqihuoxuehuatan Decoction treated group and nifedipine treated group. After fed for twelve weeks, all animals were killed to take blood sample through heart to measure , and to take aortic to determine the percentage of aortic lesions covering the intimal surface and to observe structure with light microscope ,and coronary arteria sample to observe structure with light microscope.
Results:
1. Feeding high cholesterol diet supplemented by bovine serum albumin injection bolus can establish an atherosclerotic rabbit model.
2. Buqihuoxuehuatan Decoction can decrease the aortic atherosclerosis (P < 0.05 ) .
3. Buqihuoxuehuatan Decoction can increase the serum high-density lipoprotein-cholesterol apolipoprotein A1 and plasma nitric oxide, and decrease the serum total cholesterol, low-density lipoprotein-cholesterol, apolipoprotein B and the plasma endothlin-1 (P<0.05, P<0.01) .
Conclusion:
Buqihuoxuehuatan Decoction had antiatherogenic effects and its mechanism might associate with modifying the serum lipid , preserving endothelial function and maintaining the balance of NO and ET-1.
通过动物实验观察补气活血化痰汤抗兔动脉粥样硬化斑块形成的作用及其对血浆内皮素—1(ET—1)和一氧化氮(NO)及血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL—C)、低密度脂蛋白胆固醇(LDL—C)、载脂蛋白A—1(ApoA—1)、载脂蛋白B(ApoB)水平的影响。
方法
采用免疫损伤加高胆固醇饮食方法建立新西兰大耳兔动脉粥样硬化模型，设立硝苯吡啶对照，观察补气活血化痰汤对动脉粥样硬化模型兔主动脉、冠状动脉粥样硬化病变及血脂、血浆NO、ET—1水平的影响。光镜下观察模型兔主动脉、冠状动脉的病变程度，酶法测定血脂、血浆NO水平，放射免疫法测定血浆ET—1含量。
结果
1．免疫损伤合并高胆固醇喂饲可诱发模型兔主动脉AS病变产生。
2．补气活血化痰汤能使模型兔主动脉AS病变减轻(P＜0.05)。
3．补气活血化痰汤能使ApoA—1、HDL—C、NO水平上升(P＜0.05、P＜0.01)，能使LDL—C、TC、ApoB、ET-1水平下降(P＜0.05、P＜0.01)。
结论
中药补气活血化痰汤具有较好的抗动脉粥样硬化作用，这可能与其能够有效地调节NO／ET-1平衡失调及血脂水平有关。
Objective:
To investigate the antiatherogenetic activity of Chinese medicine Buqihuoxuehuatan decoction in male rabbit fed an atherogenic diet and the effect of the total cholesterol, triglycerides, low-density lipoprotein-cholesterol apolipoprotein B high- density lipoprotein- cholesterol and apolipoprotein Al level in serum, and investigate the nitric oxide and endothlin-1 level in plasma.
Materials and Methods:
An atherosclerotic rabbit model was established by feeding high cholesterol diet supplemented by bovine serum albumin injection bolus. The rabbits were randomly divided into three groups: the model group, Buqihuoxuehuatan Decoction treated group and nifedipine treated group. After fed for twelve weeks, all animals were killed to take blood sample through heart to measure , and to take aortic to determine the percentage of aortic lesions covering the intimal surface and to observe structure with light microscope ,and coronary arteria sample to observe structure with light microscope.
Results:
1. Feeding high cholesterol diet supplemented by bovine serum albumin injection bolus can establish an atherosclerotic rabbit model.
2. Buqihuoxuehuatan Decoction can decrease the aortic atherosclerosis (P < 0.05 ) .
3. Buqihuoxuehuatan Decoction can increase the serum high-density lipoprotein-cholesterol apolipoprotein A1 and plasma nitric oxide, and decrease the serum total cholesterol, low-density lipoprotein-cholesterol, apolipoprotein B and the plasma endothlin-1 (P<0.05, P<0.01) .
Conclusion:
Buqihuoxuehuatan Decoction had antiatherogenic effects and its mechanism might associate with modifying the serum lipid , preserving endothelial function and maintaining the balance of NO and ET-1.
引文
[1] 陈灏珠主编．实用内科学(M)．第十一版．北京：人民卫生出版社，2001．1360．
[2] 郭鹞主编．人类疾病的动物模型(M)．第一版．北京：人民卫生出版社，1982．129～134．
[3] Noll G, Luscher TF. Comparative pharmacological properties among caleium channel blockers: T-channel versus L-channel blockade. Cardiology (J), 1998, 89(Supple 1): 10～15.
[4] Kiowski W, Luscher TF, Linder L, et al. Endothelin-1-induced vasoconstriction in humans. Reversal by calcium channel blockade but not by nitrovasodilators or endothelium-derived relaxing factor. Circulation (J), 1991, 83(2): 469～475.
[5] Parmley WW. Vascular protection from atherosclerosis: potential of calcium antagonists. AM J Caardial(J), 1990, 66(21): 161～221.
[6] Nayler WG. Review of preclinical data of calcium channel blockers and atherosclerosis. J Cardiovasc Pharmacol(J), 1999, 33 (Suppl 2): S7～11.
[7] Henry PD, Bentley KL. Suppression of atheroslerosis in cholesterol fed rabbit treated with nifidipine. J Clin Invert (J), 1981, 68(1): 366～369.
[8] Lichtlen PR, Hugenholtz PG, Rafflenbeul W, et al. Retardation of aniographic progression of coronary artery disease by nifedipine. Lancet(J), 1990, 335: 1109～1113.
[9] Loaldi A, Polese A, Montorsi P, et al. Comparison of nifedipine, propranolol and isosorbide dinitrate on angiographic progression and regression of coronary arterial narrowings in angina pectoris. Am J Cardiol (J), 1989; 64(8): 433～439.
[10] Schroeder Js, Gao SZ, Alderman EL, et al. A preliminary study of diltiazem in the prevention of coronary artery disease in heart-transplant recipients. N Eng J MED(J), 1993, 328: 164～170.
[11] Mehra MR, Ventura HO, Smart FW, et al. An intravascular ultrasound study of the influence of angiotension converting enzyme inhibitors and calcium entry blockers on the development of cardiac allograft vasculothy. AM J Cardiol
(J)，1995，75：853～854．
[12] 陈黎明，赵熙，岳淑敏．动脉粥样硬化与中医药治疗的途径和方法．云南中医学院学报(J)，1998，21(4)：25～26．
[13] 黄伟毅，陈素云，邱幸生．抗动脉粥样硬化的中医药研究进展．中医药研究(J)，1998，14(5)：58～61．
[14] 王吉耀．内科学(M)．第一版．北京：人民卫生出版社，2002．245～252．
[15] Blackburn H, Taylor HL, Keys A. Coronary heart disease in sewen countries. ⅩⅥ. The electrocardiogram in prediction of five-year coronary heart disease incidence among men aged forty through fifty-nine. Circulation(J), 1970, 41 (Suppl 4): I154-161.
[16] 刘秉文．血浆甘油三酯与动脉粥样硬化．心血管病学进展(J)．1999，20(1)：3～6．
[17] 郭志刚．甘油三酯代谢在动脉粥样硬化发生中的作用．心血管病进展(J)．1998，19(5)：295～297．
[18] Phillips NR, Waters D, Havel RJ. Plasma tipoproteins and pcogression of coronary artery disease evaluated by angiography and clinical events. Circulations(J), 1993, 88(6): 2762～2770
[19] Badimon JJ, Badimon L, Fuster V. Regression of atherosclerotic lesions by high density lipoprotein plasma fraction in the cholesterol-fed rabbit. J Clin Invest(J), 1990, 85 (4): 1234～1242.
[20] Eisenberg S. High density lipoprotein metabolism. J Lipid Res(J), 1984, 25(10): 1017～1058.
[21] Kuhn FE. Mohler ER, Satlet LF, et al. Effects of high-density lipoprotein on acetylcholine-induced coronary vasoreactivity, Am J Cardiol(J), 1991, 68(15): 1425～1430.
[22] Aoyama T, Yui Y, Morishita H, et al. Prostaglandin I2 half-life regulated by high density lipoprotein is decreased in acute myocardial infaretion and unstable angina pectoris. Circulation(J), 1990, 81(6): 1784～91.
[23] Mackness MI, Abbott C, Arrol S, et al. The role of high-density lipoprotein and lipid-soluble antioxidant vitamins in inhibiting low-density lipoprotein oxidation. Biochem J (J), 1993, 294(Pt3): 829～834.
[24] 李健斋，陈雯丽，马正中等．尸检冠状动脉粥样硬化与生前血脂水平的相关分析。中华心血管病杂志(J)，1996，24(4)：278～281．
[25] Thorne S. A., Abbot S. E., Winyard P. FG., et al. Extent of oxidative modification of low density lipoproteins the degree of cytotoxicity to human coronary artery cells, Heart(J), 1996, 75: 11～19
[26] Schwartz C. J., Valente A. J., and Sprague E. A.. A modern view of athero genesis. Am. J. Cardiol(J), 1993, 71: 1132～1143.
[27] Zhao Y, Sparks DL, Marcel YL. Specific phospholipid association with apolipoprotein A-I stimulates cholesterol efflux from human fibroblasts. Studies with reconstituted sonicated lipoproteins. J Biol Chem(J), 1996, 271(41): 25145～25155.
[28] Huang Y, von Eckardstein A, Wu S, Assmann G. Choleslerol efflux, cholesterol esterification, and cholesteryl ester transfer by LpA-Ⅰ and LpA-Ⅰ/A-Ⅱ in native plasma. Arterioscler Thromb Vasc Biol(J), 1995, 15(9): 1412～1418.
[29] Li Jian,. JiangLei, LiuQinghua. Protective effect of apolipoprotein AⅠ、AⅡ、and CⅡ on endothelial cells injury induced by low dencity lipoprotein. Chin Med J(J), 1998, 111: 78～81.
[30] 黎健、蒋雷、刘清华．载脂蛋白A1保护内皮细胞的实验研究。生物化学与生物物理进展(J)，1997，24：344～347．
[31] Yanagisawa M, Kurihara H, Krimurs S, et al. A novel potent wasconstrictor peptide produced by endothelialcells. Nature(J), 1988, 332: 411～415.
[32] Jones LG. Inhibition of cyclic AMP accumulation by endothelin is pertussis toxin sensitive and calcium independent in isolated adult feline cardiac myocytes. Life Sci(J), 1996, 58(2): 115～123.
[33] Alberts GF, Peifley KA, Johns A, et al. Constitutive endothelin-1 overexpression promotes smooth muscle cell proliferation via an external autocrine loop. J Biol Chem(J), 1994, 269(13): 10112～10118.
[34] Cannan CR, Burnett JC Jr, Brandt RR, et al. Endothelin a(?) pathophysiological concentrations mediates coronary vasoconstrictionvia the endotbelin-A receptor. Circulation (J), 1995, 92(11): 3312～3317.
[35] Lerman A, Holmes DR Jr, Bell MR, et al. Endothelin in coronary endothelial dysfunction and early atherosclerosis in humans. Circulation (J), 1995, 92(9): 2426～2431.
[36] 赵航，苏家灿．内皮素与冠状动脉粥样硬化．医学综述(J)，1998，4(9)：475～477．
[37] Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Mec(J), 1993, 329(27): 2002～2012.
[38] Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev (J), 1991, 43(2): 109～142.
[39] Nakatsuka M, Osawa Y. Selective inhibition of the 12-lipoxygenase pathway of arachidonic acid metabolism by L-arginine or sodium nitroprusside in intact human platelets. Biochem Biophys Res Commun(J), 1994, 200(3): 1630～1634.
[40] Tsao PS, Lewis NP, Alpert S, et al. Exposure to shear stress alters endothelial adhesiveness. Role of nitric oxide. Circulation(J), 1995, 92(12): 3513～3519.
[41] 曾晓华．一氧化氮在动脉粥样硬化中作用的研究进展．国外医学．老年医学分册(J)，1998，19(4)：158～162．
[2] 郭鹞主编．人类疾病的动物模型(M)．第一版．北京：人民卫生出版社，1982．129～134．
[3] Noll G, Luscher TF. Comparative pharmacological properties among caleium channel blockers: T-channel versus L-channel blockade. Cardiology (J), 1998, 89(Supple 1): 10～15.
[4] Kiowski W, Luscher TF, Linder L, et al. Endothelin-1-induced vasoconstriction in humans. Reversal by calcium channel blockade but not by nitrovasodilators or endothelium-derived relaxing factor. Circulation (J), 1991, 83(2): 469～475.
[5] Parmley WW. Vascular protection from atherosclerosis: potential of calcium antagonists. AM J Caardial(J), 1990, 66(21): 161～221.
[6] Nayler WG. Review of preclinical data of calcium channel blockers and atherosclerosis. J Cardiovasc Pharmacol(J), 1999, 33 (Suppl 2): S7～11.
[7] Henry PD, Bentley KL. Suppression of atheroslerosis in cholesterol fed rabbit treated with nifidipine. J Clin Invert (J), 1981, 68(1): 366～369.
[8] Lichtlen PR, Hugenholtz PG, Rafflenbeul W, et al. Retardation of aniographic progression of coronary artery disease by nifedipine. Lancet(J), 1990, 335: 1109～1113.
[9] Loaldi A, Polese A, Montorsi P, et al. Comparison of nifedipine, propranolol and isosorbide dinitrate on angiographic progression and regression of coronary arterial narrowings in angina pectoris. Am J Cardiol (J), 1989; 64(8): 433～439.
[10] Schroeder Js, Gao SZ, Alderman EL, et al. A preliminary study of diltiazem in the prevention of coronary artery disease in heart-transplant recipients. N Eng J MED(J), 1993, 328: 164～170.
[11] Mehra MR, Ventura HO, Smart FW, et al. An intravascular ultrasound study of the influence of angiotension converting enzyme inhibitors and calcium entry blockers on the development of cardiac allograft vasculothy. AM J Cardiol
(J)，1995，75：853～854．
[12] 陈黎明，赵熙，岳淑敏．动脉粥样硬化与中医药治疗的途径和方法．云南中医学院学报(J)，1998，21(4)：25～26．
[13] 黄伟毅，陈素云，邱幸生．抗动脉粥样硬化的中医药研究进展．中医药研究(J)，1998，14(5)：58～61．
[14] 王吉耀．内科学(M)．第一版．北京：人民卫生出版社，2002．245～252．
[15] Blackburn H, Taylor HL, Keys A. Coronary heart disease in sewen countries. ⅩⅥ. The electrocardiogram in prediction of five-year coronary heart disease incidence among men aged forty through fifty-nine. Circulation(J), 1970, 41 (Suppl 4): I154-161.
[16] 刘秉文．血浆甘油三酯与动脉粥样硬化．心血管病学进展(J)．1999，20(1)：3～6．
[17] 郭志刚．甘油三酯代谢在动脉粥样硬化发生中的作用．心血管病进展(J)．1998，19(5)：295～297．
[18] Phillips NR, Waters D, Havel RJ. Plasma tipoproteins and pcogression of coronary artery disease evaluated by angiography and clinical events. Circulations(J), 1993, 88(6): 2762～2770
[19] Badimon JJ, Badimon L, Fuster V. Regression of atherosclerotic lesions by high density lipoprotein plasma fraction in the cholesterol-fed rabbit. J Clin Invest(J), 1990, 85 (4): 1234～1242.
[20] Eisenberg S. High density lipoprotein metabolism. J Lipid Res(J), 1984, 25(10): 1017～1058.
[21] Kuhn FE. Mohler ER, Satlet LF, et al. Effects of high-density lipoprotein on acetylcholine-induced coronary vasoreactivity, Am J Cardiol(J), 1991, 68(15): 1425～1430.
[22] Aoyama T, Yui Y, Morishita H, et al. Prostaglandin I2 half-life regulated by high density lipoprotein is decreased in acute myocardial infaretion and unstable angina pectoris. Circulation(J), 1990, 81(6): 1784～91.
[23] Mackness MI, Abbott C, Arrol S, et al. The role of high-density lipoprotein and lipid-soluble antioxidant vitamins in inhibiting low-density lipoprotein oxidation. Biochem J (J), 1993, 294(Pt3): 829～834.
[24] 李健斋，陈雯丽，马正中等．尸检冠状动脉粥样硬化与生前血脂水平的相关分析。中华心血管病杂志(J)，1996，24(4)：278～281．
[25] Thorne S. A., Abbot S. E., Winyard P. FG., et al. Extent of oxidative modification of low density lipoproteins the degree of cytotoxicity to human coronary artery cells, Heart(J), 1996, 75: 11～19
[26] Schwartz C. J., Valente A. J., and Sprague E. A.. A modern view of athero genesis. Am. J. Cardiol(J), 1993, 71: 1132～1143.
[27] Zhao Y, Sparks DL, Marcel YL. Specific phospholipid association with apolipoprotein A-I stimulates cholesterol efflux from human fibroblasts. Studies with reconstituted sonicated lipoproteins. J Biol Chem(J), 1996, 271(41): 25145～25155.
[28] Huang Y, von Eckardstein A, Wu S, Assmann G. Choleslerol efflux, cholesterol esterification, and cholesteryl ester transfer by LpA-Ⅰ and LpA-Ⅰ/A-Ⅱ in native plasma. Arterioscler Thromb Vasc Biol(J), 1995, 15(9): 1412～1418.
[29] Li Jian,. JiangLei, LiuQinghua. Protective effect of apolipoprotein AⅠ、AⅡ、and CⅡ on endothelial cells injury induced by low dencity lipoprotein. Chin Med J(J), 1998, 111: 78～81.
[30] 黎健、蒋雷、刘清华．载脂蛋白A1保护内皮细胞的实验研究。生物化学与生物物理进展(J)，1997，24：344～347．
[31] Yanagisawa M, Kurihara H, Krimurs S, et al. A novel potent wasconstrictor peptide produced by endothelialcells. Nature(J), 1988, 332: 411～415.
[32] Jones LG. Inhibition of cyclic AMP accumulation by endothelin is pertussis toxin sensitive and calcium independent in isolated adult feline cardiac myocytes. Life Sci(J), 1996, 58(2): 115～123.
[33] Alberts GF, Peifley KA, Johns A, et al. Constitutive endothelin-1 overexpression promotes smooth muscle cell proliferation via an external autocrine loop. J Biol Chem(J), 1994, 269(13): 10112～10118.
[34] Cannan CR, Burnett JC Jr, Brandt RR, et al. Endothelin a(?) pathophysiological concentrations mediates coronary vasoconstrictionvia the endotbelin-A receptor. Circulation (J), 1995, 92(11): 3312～3317.
[35] Lerman A, Holmes DR Jr, Bell MR, et al. Endothelin in coronary endothelial dysfunction and early atherosclerosis in humans. Circulation (J), 1995, 92(9): 2426～2431.
[36] 赵航，苏家灿．内皮素与冠状动脉粥样硬化．医学综述(J)，1998，4(9)：475～477．
[37] Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Mec(J), 1993, 329(27): 2002～2012.
[38] Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev (J), 1991, 43(2): 109～142.
[39] Nakatsuka M, Osawa Y. Selective inhibition of the 12-lipoxygenase pathway of arachidonic acid metabolism by L-arginine or sodium nitroprusside in intact human platelets. Biochem Biophys Res Commun(J), 1994, 200(3): 1630～1634.
[40] Tsao PS, Lewis NP, Alpert S, et al. Exposure to shear stress alters endothelial adhesiveness. Role of nitric oxide. Circulation(J), 1995, 92(12): 3513～3519.
[41] 曾晓华．一氧化氮在动脉粥样硬化中作用的研究进展．国外医学．老年医学分册(J)，1998，19(4)：158～162．