重组RGD肽水蛭素改善大鼠冠脉微循环及其机制的研究

The Protective Effect of a New Thrombin Inhibitor on the Coronary Microthrombosis Induced by Sodium Laurate

目的观察双重组RGD肽水蛭素对大鼠冠脉微循环障碍的疗效 ,并探讨其作用机理。方法健康雄性SD大鼠共62只 ,随机分为正常对照组 (n=6)、安慰剂组 (n=18)以及RGD肽水蛭素治疗组(n=36) ,后者根据所用RGD肽水蛭素剂量进一步分为1mg/kg和5mg/kg体质量2个亚组 ,每组各18只。RGD肽水蛭素于建模当日采用腹腔注射的方法给药 ,以注射生理盐水做为安慰剂。分别采用病理切片、超声心动图和彩色微粒子测量技术 ,观察各组大鼠心肌内微血栓和微梗死形成 ,以及心功能和心肌局部血流量变化的情况 ;采用免疫组化和RT -PCR的方法观察心肌组织内IL -18蛋白及mRNA的表达。结果与安慰剂组相比 ,1mg/kg/d及5mg/kg/d的RGD肽水蛭素可显著减少大鼠心肌内微栓塞数量以及局部梗死面积 (P<0.01) ,同时大鼠心功能LVEF和心肌局部血流量也明显得到改善 ;RGD肽水蛭素也显著下调大鼠心肌组织内IL -18蛋白和mRNA的表达 (P<0.05)。结论RGD肽水蛭素能明显改善大鼠因微栓塞所致的冠脉微循环障碍 ,可作为治疗冠脉微循环障碍的重要药物。其中抑制IL -18的分泌表达 ,可能是RGD肽水蛭素抗炎改善冠脉微循环的重要机制之一。

Objective To examine the preventive effect of r-RGD-Hirudin,a thrombin inhibitor,on the coronary microthrombosis induced by sodium laurate in rats.Methods62male Sprague-Dawley rats were used in the present study.The microthrombosis model was established and r-RGD-Hirudin,1or5mg/kg was adminisˉtered intraperitoneally5minutes after the injection of sodium laurate,in the control group saline was injected inˉstead.Results The microthrombosis in the coronary arterioles was successfully induced and the administration of r-RGD-Hirudin,(1and5mg/kg)significantly reduced the area and number of minor myocardial infarction(P<0.01).RT-PCR showed that IL-18in the myocardium was markedly increased after the operation and r-RGD-hirudin significantly decreased the IL-18expression.Conclusions The present study shows that r-RGD-Hirudin might be beneficial in the treatment of minor myocardial infarction caused by microthrombosis.