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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 observe the curative effect of RGD-peptide-hirudin on coronary microcirculation disturbance in rats and its mechanism of action. Methods Sixty-two healthy male Sprague-Dawley rats were randomly divided into normal control group (n = 6), placebo group (n = 18) and RGD peptide hirudin treatment group (n = 36) The prime dose was further divided into 2 subgroups of 1 mg / kg and 5 mg / kg of body weight, with 18 in each group. RGD peptide hirudin was administered intraperitoneally on the day of modeling with saline as a placebo. Pathological sections, echocardiography and color microparticle measurement techniques were used to observe the formation of micro-thrombus and micro-infarction in myocardium and the changes of cardiac function and myocardial blood flow in each group. Immunohistochemistry and RT-PCR The expression of IL-18 protein and mRNA in myocardium was observed. Results Compared with the placebo group, 1mg / kg / d and 5mg / kg / d of RGD peptide hirudin significantly reduced the number of myocardial microembolization and infarct size in rats (P <0.01), meanwhile, LVEF And myocardial blood flow were also significantly improved; RGD peptide also significantly decreased myocardial IL-18 protein and mRNA expression (P <0.05). Conclusion RGD peptide Hirudin can obviously improve the microcirculation disturbance caused by micro-embolism in rats, and can be used as an important drug for the treatment of coronary microcirculation disorder. Among them, the inhibition of the secretion of IL-18 may be one of the important mechanisms by which RGD peptide Hirudin anti-inflammatory can improve coronary microcirculation.