蛇毒PCA改善冠脉微血栓大鼠血液流变学的机制研究  

Agkistrodon halys venom PCA improves hemorheology in rats with coronary artery microthrombosis

作　　者：李曙[1] 张根葆[1,2] 洪云[3] 陆晓华[4] 

机构地区：[1]皖南医学院病理生理学教研室,安徽芜湖241002 [2]皖南医学院蛇毒研究所,安徽芜湖241002 [3]皖南医学院弋矶山医院超声医学科,安徽芜湖241002 [4]皖南医学院机能实验中心,安徽芜湖241002

出　　处：《中国病理生理杂志》2012年第4期595-600,共6页Chinese Journal of Pathophysiology

基　　金：安徽省高等学校省级自然科学研究项目(No.KJ2010B461);安徽省教育厅自然基金重点项目(No.KJ2011266);皖南医学院中青年课题(No.WK200918)

摘　　要：目的:探讨皖南产蝮蛇毒(AHV)蛋白C激活物(PCA)改善冠脉微血栓(CAM)大鼠血液流变学的作用机制。方法:Sprague-Dawley大鼠50只,随机分为假手术组、CAM组、低、中、高剂量PCA[CAM+PCA(0.5mg/kg)、CAM+PCA(2 mg/kg)、CAM+PCA(8 mg/kg)]干预组,每组10只。通过从主动脉根部直接向左心室注入月桂酸钠1.0 mg/kg(浓度10 g/L)以建立大鼠冠脉微血栓模型,采用血栓弹力仪系统(TEG)描计血栓弹力图,测定各组血浆中内皮素-1(ET-1)、P-选择素(P-selectin)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)和天冬氨酸氨基转移酶(AST)的水平;Western blotting检测心肌组织中P-selectin和肿瘤坏死因子α(TNF-α)蛋白表达;光镜观察心肌组织学改变。结果:与模型组比较,PCA大剂量干预组凝血时间和血凝块形成时间延长,Alpha角度、最大幅度和血凝指数值减小(P<0.05),血浆CK-MB、LDH、AST、ET-1和P-selectin的水平降低(P<0.05),心肌组织P-selectin和TNF-α的蛋白表达下降(P<0.05)。病理观察显示中、高剂量PCA干预组大鼠冠脉未形成微血栓。结论:蝮蛇毒PCA组分可以限制冠脉微血栓的形成,降低血浆ET-1和P-selectin的含量,抑制心肌组织P-selectin和TNF-α表达,改善微血栓后血液流变学变化,有效保护心肌细胞。AIM： To explore the effect of protein C activator（PCA） from Wannan Agkistrodon halys venom on hemorheology in the rats with coronary artery microthrombosis（CAM）.METHODS： Fifty SD rats were randomly divided into sham operation group,CAM group,low dose（0.5 mg/kg）,medium dose（2 mg/kg） and high dose（8 mg/kg） of PCA treatment groups.The model of CAM was induced by injecting sodium laurate at dose of 1.0 mg/kg with the concentration of 10 g/L from aortic root to left ventricle.Thrombelastogram was obtained by thromboelastography instrument system.The content of endothelin-1（ET-1） and P-selectin,and the activity of creatine kinase-MB（CK-MB）,lactate dehydrogenase（LDH） and aspartate aminotransferase（AST） in plasma were determined by ELISA.The protein expression of myocardial P-selectin and TNF-α was detected by Western blotting.The structural changes of the myocardial cells and interstitial tissues were observed under microscope.RESULTS： Compared with CAM group,clotting time and clot formation time significantly prolonged in high-dose PCA group.The alpha angle,maximum amplitude,coagulation index,and the levels of ET-1,P-selectin,CK-MB,LDH and AST in plasma were decreased.The protein expression levels of P-selectin and TNF-α in myocardial tissues were down-regulated（P0.05）.Cardiac histological observation showed that coronary microthrombi in medium-dose and high-dose PCA groups were not found.CONCLUSION： Agkistrodon halys venom PCA inhibits the formation of coronary microthrombi,down-regulates the expression of P-selectin and TNF-α,improves the abnormal hemorheology after microthrombi,and effectively protects myocardial cells.

关 键 词：蝮蛇毒 蛋白C激活物 微血栓 血液流变学 

分 类 号：R543.3[医药卫生—心血管疾病]