蝮蛇毒蛋白C激活物改善急性心肌梗死大鼠心功能的机制研究  

Study on mechanisms of Agkistrodon halyx pallas venom PCA to improve heart function in rats with acute myocardial infarction

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 [2]皖南医学院蛇毒研究所 [3]皖南医学院弋矶山医院超声医学科 [4]皖南医学院机能实验中心

出　　处：《中国临床药理学与治疗学》2012年第2期141-146,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：安徽省高等学校省级自然科学研究项目(KJ2010B461);安徽省科技厅科技项目(10021303009);皖南医学院中青年课题(WK200918)

摘　　要：目的:探讨皖南产蝮蛇毒(AHV)蛋白C激活物(protein C activator,PCA)改善急性心肌梗死大鼠心功能作用与机制。方法:Sprague-Daw-ly大鼠60只,随机分为假手术(SH)组、心肌梗死模型(MI)组、PCA低、中、高剂量组(0.5、2、8mg/kg)、阳性对照组(阿司匹林5mg/kg),每组10只。通过结扎冠状动脉前降支建立急性心肌梗死(AMI)模型,采用Medlab生物信号处理系统监测大鼠心脏血流动力学变化。Westernblot检测心肌基质金属蛋白酶-9(MMP-9)蛋白表达;光镜观察心肌组织学改变。结果:与心肌梗死组比较,PCA高、中剂量大鼠左室内压最低值(LVDP)、左心室舒张末期压(LVEDP)、左心室压力最大上升速率(+dp/dtmax)、左心室压力最大下降速率(-dp/dtmax)明显升高(P<0.05),MMP-9的蛋白表达下降(P<0.05)。病理观察显示PCA干预组较梗死模型组炎症细胞浸润显著减轻,梗死面积缩小。结论:蝮蛇毒PCA组分可以限制急性心肌梗死早期心肌梗死扩大,有效改善心脏血液动力学,抑制MMP-9表达,对急性心肌梗死后心室重构有一定的干预作用。AIM： To explore the effect of protein C activator（PCA） from Wannan Agkistro- don halyx pallas venom on heart function in rats with acute myocardial infarction and its mechanism. METHODS： Sixty SD rats were randomly divided into sham operation （SH） group, myo- cardial infarct （MI） group, low dose, medium dose and high dose of PCA groups （0. 5,2, 8 mg/kg） and aspirin group （5 mg/kg）, and ten in each group. Through ligating of the anterior descending coronary artery to establish AMI,the cardiac muscle samples were obtained 12 hours after AMI. Medlab bio-signal processing system monitored hemodynamic changes in rat heart. The expression of myocardial MMP-9 was detected by Western blot. Myocardial cell and intersti tial tissue were observed by microscope. RESULTS：Compared with myocardial infarct group rats, high dose and medium dose PCA significantly increased LVDP, LVEDP, significantly increased ＋dp/dtm^x and --dp/dt and reduced levels of MMP-9 protein expression （P d0.05）. Cardiac histological detection showed that PCA significantly reduced in infiltration of inflammatory cells and infarct size compared with AMI group. CONCLUSION： Agkistrodon halyx pallas venom PCA can limit the expansion of early myocardial infarction, improve cardiac hemodynamics, inhibit expression of MMP-9, so it would have a certain intervention effect on ventricular remodeling after acute myocardial infarction.

关 键 词：蝮蛇毒 蛋白C激活物 心肌梗死 心室重构 基质金属蛋白酶 

分 类 号：R965.2[医药卫生—药理学]