脉通方对高糖高脂高胆固醇饮食DM大鼠脂代谢及股动脉形态的影响
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摘要
目的：研究脉通方对引起糖尿病下肢动脉硬化闭塞症相关因素的影响，主要是糖代谢、脂代谢、氧化应激及血小板功能的影响。方法：采用高糖高脂高胆固醇喂养SD大鼠，并用Alloxan腹腔注射诱发糖尿病大鼠模型。随机分为脉通方低、高剂量组，西洛他唑组、模型对照组，并设正常对照组。通过放射免疫、生化检测、形态学等方法，对照观察各组药物对DN大鼠一般状态、血糖、血清胰岛素、TC、TG、HDL-C、Lp(a)、SOD、MDA、TXB_2、6-Keto-PGF_1。等指标及股动脉组织形态学的影响。结果：DM大鼠存在大部分指标明显异常及股动脉病理改变，脉通方可改善一般状态、纠正糖、脂代谢紊乱，增强细胞抗氧化能力，改善血小板聚集功能。综合疗效优于西药。结论：脉通方通过多环节、多途径的调节作用，减少或抑制脂质在动脉内膜堆积，有效地保护血管内皮细胞结构的完整性，防止动脉血管痉挛和血栓形成，从而起到防治DLASO的作用。
Objective: To investigate the affection of Maitongfang on certain related factors which can cause DLASO, mainly on the affection on glycometabolism, lipometabolism, oxidative stress and function of blood platelet. Methods: The SD rats were fed with high-sugar, high-fat and high-cholesterol feeding stuff, and then induced by Alloxan intraperitoneally to be diabetic rat models. The rats were randomly divided into five groups, ie. Model control, low dosage of Maitongfang, high dosage of Maitongfang, and Cilostazol group respectively. Normal control group was also established. The effect of different medicines on the following parameters were detected by radioimmunoassay, biochemistry detect method, Histomorphometry, etc. which were serum level of insulin, TC, TG, HDL-C, Lp(a), SOD, MDA, TXB2, 6-Keto-PGF_(1a), tectology of femoral artery, changes in general condition and blood glucose as well. Results: The abnormalities of most of the parameters stated above were shown in DM rats, as well as the pathologic changes of femoral artery. While Maitongfang demonstrates the action of improving the general condition, regulating the metabolism of blood glucose and blood lipid, strengthening the cell's ability of antioxidation, improving the function of platelet aggregation. The comprehensive curative effect of Maitongfang is superior to that of Cilostazol group. Conclusion: Through the regulating action of many pathways and links which presented as decreasing or inhibiting accumulation of lipid on Tunica intima of artery, protecting the integrity of the structure of blood vessel endothelial cell effectively, preventing artery vessel spasm and formation of thrombosis, Maitongfang contributes to the prevention and treatment of DLASO.
Objective: To investigate the affection of Maitongfang on certain related factors which can cause DLASO, mainly on the affection on glycometabolism, lipometabolism, oxidative stress and function of blood platelet. Methods: The SD rats were fed with high-sugar, high-fat and high-cholesterol feeding stuff, and then induced by Alloxan intraperitoneally to be diabetic rat models. The rats were randomly divided into five groups, ie. Model control, low dosage of Maitongfang, high dosage of Maitongfang, and Cilostazol group respectively. Normal control group was also established. The effect of different medicines on the following parameters were detected by radioimmunoassay, biochemistry detect method, Histomorphometry, etc. which were serum level of insulin, TC, TG, HDL-C, Lp(a), SOD, MDA, TXB2, 6-Keto-PGF_(1a), tectology of femoral artery, changes in general condition and blood glucose as well. Results: The abnormalities of most of the parameters stated above were shown in DM rats, as well as the pathologic changes of femoral artery. While Maitongfang demonstrates the action of improving the general condition, regulating the metabolism of blood glucose and blood lipid, strengthening the cell's ability of antioxidation, improving the function of platelet aggregation. The comprehensive curative effect of Maitongfang is superior to that of Cilostazol group. Conclusion: Through the regulating action of many pathways and links which presented as decreasing or inhibiting accumulation of lipid on Tunica intima of artery, protecting the integrity of the structure of blood vessel endothelial cell effectively, preventing artery vessel spasm and formation of thrombosis, Maitongfang contributes to the prevention and treatment of DLASO.
引文
[1] 李仕明．糖尿病足与相关并发症的诊治．第1版．北京：人民卫生出版社，2002；序
[2] 胡绍文，郭瑞林．实用糖尿病学。第1版。北京：人民军医出版社，1998；211
[3] 袁戈恒，高妍，冯琦，等．西洛他唑治疗2型糖尿病下肢血管病变的临床观察．中国临床药理学杂志，1999；15(6)：421
[4] 郑杭玲，吴天凤，吴金彦．西洛他唑对老年血栓性疾病患者血小板聚集功能的影响。浙江医学，2000；22(12)：715
[5] 肖万泽．糖尿病的中西医诊断与治疗．第1版．北京：中国医药科技出版社，1999；167
[6] 张伯臾。中医内科学．第1版。上海：上海科学技术出版社，1989；250
[7] 林兰．中西医结合糖尿病学．第1版．北京：中国医药科技出版社，1999，366-367
[8] 林兰．中西医结合糖尿病学．第1版．北京：中国医药科技出版社，1999，211-212
[9] 张愍，尹丙生．中西医结合高脂血症治疗学．第1版．北京：人民军医出版社，2001；281-287
[10] 赵克然，杨毅军，曹道俊．氧自由基与临床．第1版．北京：中国医药科技出版社，2000；569-583
[11] 张涛，杜兰萍，崔萍，等．水蛭和丹参对血管成形术后平滑肌细胞增殖影响的实验研究．中国中西医结合杂志，1998；18(3)：159-161
[12] 孙子林，葛祖凯．糖尿病动物模型及其进展．中国糖尿病杂志，1999；7(4)：227-228
[13] Deniel Porte,Jr.Roberts,Sherwin．埃伦保-里弗金斯糖尿病学．英文影印版．第5版．科学出版社，2000；301
[14] 李日焕．中草药抗动脉粥样硬化实验研究概况．右江民族医学院学报，1990；12(3)：61-63
[15] 周青，徐天蓉，天成功，等．实验性糖尿病血管病变病理形态研究．江苏
医药，1996；22(9)：597-599
[16] 袁戈恒，高妍，冯琦，等．西洛他唑治疗2型糖尿病下肢血管病变的临床观察．中国临床药理学杂志，1999；15(6)：421-424
[17] Rodriguez-Manasl, Angulo J, Peirol, etal. Endothelial dys function and metabolic control in streptozocin-induced rats. Br J Pharmacol 1998;123:1495
[18] Caballero AE, Arora S, Saouaf R,etal. Micro vascular and macro vascular reactivity is reduced in subjects at risk for type 2 diabetes. Diabetes, 1999;48:1856
[19] Jensen-Urstad, KJ, ReichardPG, RosforsJS, etal. Early athero sclerosis is retarded byimproved long-term blood glucose contro l in patients with IDDM. Diabetes, 1996;45:1253
[20] 陶凯忠．高血糖与糖尿病血管病变机制．中国糖尿病杂志，2001；9(5)：306-308
[21] 吴家祥．实验性糖尿病大鼠冠状动脉早期形态变化．白求恩医科大学学报，1987；13：483
[22] 吴家祥，肖纫秋，张凤兰，等．胰岛素与动脉粥样硬化关系的实验研究．中华内分泌代谢杂志，1992；8(4)：218-221
[23] 沈捷，刘铨之，陈家伟，等．高胰岛素血症，高脂血症致动脉粥样硬化的实验研究．中国糖尿病杂志，1998；6(2)：97-100
[24] Mykkanen L, Zaccaro DJ, Halses CN. The relationship of Proinsulin and insulin to insulin sentivity and acute insulin response in subjects with newly diagnosed type 2 diabetes: the Insulin Resistance Arteriosclerosis Study. Diabetologia, 1999; 42(9):1060-1066
[25] Haffner SM, D' Agostino RJ, Mykkanen L, etal. Insulin sensitivity in subjects with type 2 diabetes. Relationship to cardiovascular risk factors: the Insulin Resistance Arteriosclerosis Study. Diabetes Care, 1999; 22(4): 562-568
[26] 尚德俊，王嘉桔，王书桂，等．中西医结合治疗闭塞性动脉硬化笔谈．
山东医药，1985；(5)：25
[27] 叶平．血脂的基础与临床．第1版．北京：人民军医出版社，2002；346
[28] 叶平．血脂的基础与临床．第1版．北京：人民军医出版社，2002；191-200
[29] 叶平．血脂的基础与临床．第1版．北京：人民军医出版社，2002；255-263
[30] 叶平．血脂的基础与临床．第1版．北京：人民军医出版社，2002；264-278
[31] 叶平．血脂的基础与临床．第1版．北京：人民军医出版社，2002；45-54
[32] 叶平．血脂的基础与临床．第1版．北京：人民军医出版社，2002；279-289
[33] 张愍，尹丙生。中西医结合高脂血症治疗学．第1版．北京：人民军医出版社，2001；79-86
[34] 刘铨之．糖尿病大血管病变发病机理的一些进展。临床荟萃，1990；5(2)：53-56
[35] 陈勇，金权膺．糖尿病中促动脉粥样硬化因素的探讨．江苏医药，1992；18(4)：179-181
[36] 谌登兵，欧造国．糖尿病大鼠血管内皮损伤的实验研究．重庆医学，1999；28(4)：245-246
[37] Ross R. N Eng IJ Med, 1986; 314:488
[38] Lorenzi M.Glucose toxicity in the vascular complications of diabetes: the cellular perspective. Diabetes Metab Rev, 1992; 8:85-103
[2] 胡绍文，郭瑞林．实用糖尿病学。第1版。北京：人民军医出版社，1998；211
[3] 袁戈恒，高妍，冯琦，等．西洛他唑治疗2型糖尿病下肢血管病变的临床观察．中国临床药理学杂志，1999；15(6)：421
[4] 郑杭玲，吴天凤，吴金彦．西洛他唑对老年血栓性疾病患者血小板聚集功能的影响。浙江医学，2000；22(12)：715
[5] 肖万泽．糖尿病的中西医诊断与治疗．第1版．北京：中国医药科技出版社，1999；167
[6] 张伯臾。中医内科学．第1版。上海：上海科学技术出版社，1989；250
[7] 林兰．中西医结合糖尿病学．第1版．北京：中国医药科技出版社，1999，366-367
[8] 林兰．中西医结合糖尿病学．第1版．北京：中国医药科技出版社，1999，211-212
[9] 张愍，尹丙生．中西医结合高脂血症治疗学．第1版．北京：人民军医出版社，2001；281-287
[10] 赵克然，杨毅军，曹道俊．氧自由基与临床．第1版．北京：中国医药科技出版社，2000；569-583
[11] 张涛，杜兰萍，崔萍，等．水蛭和丹参对血管成形术后平滑肌细胞增殖影响的实验研究．中国中西医结合杂志，1998；18(3)：159-161
[12] 孙子林，葛祖凯．糖尿病动物模型及其进展．中国糖尿病杂志，1999；7(4)：227-228
[13] Deniel Porte,Jr.Roberts,Sherwin．埃伦保-里弗金斯糖尿病学．英文影印版．第5版．科学出版社，2000；301
[14] 李日焕．中草药抗动脉粥样硬化实验研究概况．右江民族医学院学报，1990；12(3)：61-63
[15] 周青，徐天蓉，天成功，等．实验性糖尿病血管病变病理形态研究．江苏
医药，1996；22(9)：597-599
[16] 袁戈恒，高妍，冯琦，等．西洛他唑治疗2型糖尿病下肢血管病变的临床观察．中国临床药理学杂志，1999；15(6)：421-424
[17] Rodriguez-Manasl, Angulo J, Peirol, etal. Endothelial dys function and metabolic control in streptozocin-induced rats. Br J Pharmacol 1998;123:1495
[18] Caballero AE, Arora S, Saouaf R,etal. Micro vascular and macro vascular reactivity is reduced in subjects at risk for type 2 diabetes. Diabetes, 1999;48:1856
[19] Jensen-Urstad, KJ, ReichardPG, RosforsJS, etal. Early athero sclerosis is retarded byimproved long-term blood glucose contro l in patients with IDDM. Diabetes, 1996;45:1253
[20] 陶凯忠．高血糖与糖尿病血管病变机制．中国糖尿病杂志，2001；9(5)：306-308
[21] 吴家祥．实验性糖尿病大鼠冠状动脉早期形态变化．白求恩医科大学学报，1987；13：483
[22] 吴家祥，肖纫秋，张凤兰，等．胰岛素与动脉粥样硬化关系的实验研究．中华内分泌代谢杂志，1992；8(4)：218-221
[23] 沈捷，刘铨之，陈家伟，等．高胰岛素血症，高脂血症致动脉粥样硬化的实验研究．中国糖尿病杂志，1998；6(2)：97-100
[24] Mykkanen L, Zaccaro DJ, Halses CN. The relationship of Proinsulin and insulin to insulin sentivity and acute insulin response in subjects with newly diagnosed type 2 diabetes: the Insulin Resistance Arteriosclerosis Study. Diabetologia, 1999; 42(9):1060-1066
[25] Haffner SM, D' Agostino RJ, Mykkanen L, etal. Insulin sensitivity in subjects with type 2 diabetes. Relationship to cardiovascular risk factors: the Insulin Resistance Arteriosclerosis Study. Diabetes Care, 1999; 22(4): 562-568
[26] 尚德俊，王嘉桔，王书桂，等．中西医结合治疗闭塞性动脉硬化笔谈．
山东医药，1985；(5)：25
[27] 叶平．血脂的基础与临床．第1版．北京：人民军医出版社，2002；346
[28] 叶平．血脂的基础与临床．第1版．北京：人民军医出版社，2002；191-200
[29] 叶平．血脂的基础与临床．第1版．北京：人民军医出版社，2002；255-263
[30] 叶平．血脂的基础与临床．第1版．北京：人民军医出版社，2002；264-278
[31] 叶平．血脂的基础与临床．第1版．北京：人民军医出版社，2002；45-54
[32] 叶平．血脂的基础与临床．第1版．北京：人民军医出版社，2002；279-289
[33] 张愍，尹丙生。中西医结合高脂血症治疗学．第1版．北京：人民军医出版社，2001；79-86
[34] 刘铨之．糖尿病大血管病变发病机理的一些进展。临床荟萃，1990；5(2)：53-56
[35] 陈勇，金权膺．糖尿病中促动脉粥样硬化因素的探讨．江苏医药，1992；18(4)：179-181
[36] 谌登兵，欧造国．糖尿病大鼠血管内皮损伤的实验研究．重庆医学，1999；28(4)：245-246
[37] Ross R. N Eng IJ Med, 1986; 314:488
[38] Lorenzi M.Glucose toxicity in the vascular complications of diabetes: the cellular perspective. Diabetes Metab Rev, 1992; 8:85-103