噻氯匹定对鹌鹑实验性动脉粥样硬化的抑制作用及其机理  

Inhibitory effects of ticlopidine on experimental atherosclerosis in quails and its mechanism

作　　者：朱东亚[1] 邓德峰 易宏伟[1] 华维一[1] 

机构地区：[1]中国药科大学新药研究中心

出　　处：《中国药理学与毒理学杂志》1997年第4期263-266,共4页Chinese Journal of Pharmacology and Toxicology

摘　　要：用食饵性动脉粥样硬化（ＡＳ）模型，研究噻氯匹定的抗ＡＳ作用。噻氯匹定２０和６０ｍｇ·ｋｇ－１·ｄ－１连续８ｗｋ，ｐｏ，能显著抑制鹌鹑动脉内膜ＡＳ斑块形成．每２ｗｋ测定血清血脂，该药对甘油三酯，总胆固醇和低密度脂蛋白胆固醇水平无明显影响，但使高密度脂蛋白胆固醇略有升高．于ＡＳ造型２和４ｗｋ，血清ＮＯ水平下降；在ＡＳ造型６ｗｋ，ＮＯ水平升高，噻氯匹定可逆转ＡＳ造型引起的ＮＯ水平变化．用放免法分析该药对前列环素合成的影响，结果噻氯匹定３．３，１０和３０ｍｇ·ｋｇ－１，２４ｈ内ｉｇ３次，均显著提高大鼠动脉壁６－酮－前列腺素Ｆ１α含量．结果表明噻氯匹定可抑制鹌鹑实验性ＡＳ斑块形成，除抑制血小板功能外，保护内皮功能可能也是该药抑制ＡＳ病变形成的重要机理．The inhibitory effect of ticlopidine on the development of atherosclerotic lesions in quails maintained on a 1% (w/w) cholesterol enriched diet for an 8 wk period was examined. Ticlopidine was supplemented to the diet at three different levels to correspond to doses of 6.7,20 and 60 mg·kg 1 ·d 1 .The cholesterol diet increased serum levels of total cholesterol (TC),triglycerides (TG) and low density lipoprotein cholesterol (LDL C) and induced a pronounced degree of atherosclerotic lesions in aortic intimal surface.Treatment of hyperlipidemia quails with ticlopidine at dose of 20 and 60 mg·kg 1 ·d 1 resulted in a marked reduction in aortic plaque formation but not in serum levels of TC,TG and LDL C.Ticlopidine 60 mg·kg 1 ·d 1 increased serum high density lipoprotein cholesterol (HDL C) concentration compared with control quails at 6 wk. Cholesterol feeding caused a significant reduction of serum NO content at 2 and 4 wk, whereas a considerable increase in serum NO content at 6 wk, both were reversed by ticlopidine.In addition, oral administration of ticlopidine 3.3,10 and 30 mg·kg 1 resulted in a marked increase in 6 keto prostaglandin F 1α contents in carotid artery of normal rat. The results suggest that ticlopidine has an inhibitory effect on the development of atherosclerosis lesions in quails through a mechanism involving its protective effect on endothelial function.

关 键 词：噻氯区定 动脉粥样硬化 药物疗法 动物模型 

分 类 号：R972.6[医药卫生—药品] R543.505[医药卫生—药学]