法舒地尔对急性心肌梗死大鼠心肌组织中Rho激酶的影响及心肌保护作用(英文)

目的:分析急性心肌梗死(AMI)后大鼠心肌组织Rho激酶表达的变化及心肌细胞凋亡情况,观察法舒地尔对急性心肌梗死(AMI)后大鼠心肌组织Rho激酶表达的影响,探讨法舒地尔对心梗后心肌的保护作用。方法:选取雄性Wistar大鼠,随机分为三组:治疗组、AMI组、假手术组。治疗组及AMI组均结扎左前降支(LAD)制作AMI模型;假手术组只在其LAD下穿线不结扎。治疗组给予法舒地尔5mg/kg,腹腔注射,每日两次;对照组和假手术组给予等量生理盐水。1周后,EvensBlue及NBT双染色确定缺血面积及梗死面积,RT-PCR法测定rho激酶mRNA的表达,DNA断裂的原位末端标记法(T UNEL法)检测缺血区心肌细胞凋亡指数(AI),免疫组化测定凋亡相关蛋白bcl-2及bax表达的变化。结果:1周后,AMI组与假手术组相比,AMI组大鼠Rho激酶mRNA表达增加(P0.01),凋亡相关蛋白bax表达增加(P0.01),bcl-2表达减少(P0.01),AI明显增加(P0.01)。治疗组与AMI组相比,梗死面积显著减小(P0.05),Rho激酶mRNA及bax表达显著减少,AI显著降低,bcl-2表达显著增加(均P0.01)。结论:大鼠AMI后,心肌组织中Rho激酶的表达增加,心肌细胞凋亡指数增加,连续应用法舒地尔1周能有效减少心肌细胞凋亡指数,起到心肌保护的作用。

The Effects of Rho-associated Kinases in Rats with Acute MyocardialInfarction by Fasudil and its Protection of the Myocytes

Objective:To analyze the expression of Rho kinases and cardiac myocyte apoptosis status on rats of AMI, to Explorethe effect of fasudil on the Rho kinase expression, try to find the protective effect on myocardia of Fasudil after AMI.Methods:MaleWistar rats were randomly divided into three groups: the treatment group, the AMI group and the sham-operated group. The treatmentgroup and the AMI group clamped left anterior descending branch of the coronary artery. The sham group consisted of rats undergone asuture below the left anterior descending branch without clamping of the vessel. Rats in the treatment group received intra-peritoneal injectionsof 5mg/kg of Fasudil twice a day, Both the AMI group and The sham-operated groups received an equivalent normal saline injectionsonly. All rats were sacrificed one week after. Tests were performed as follows: confirmation of areas of myocardial infarction andischemia by double staining with EvensBlue and NBT, analysis of mRNA expression of Rho kinases by RT-PCR, TUNEL assay to determinethe AI in ischemia region, measurement of changes of the expression of apoptosis related proteins, bcl-2 and bax, by immunohistochemistry.Results:One week after,compared to the sham-operated group, in the AMI group, there was significant increase in the expressionof Rho kinase mRNA and apoptosis related protein bax and The AI, whereas the expression of bcl-2 was decreased (P<0.01). Comparedto the AMI group, in treatment group ,the area of infarction was significantly smaller(P<0.05), there was significant decrease in theexpression of Rho kinase mRNA and bax and The AI, while the expression of bcl-2 was increased (P<0.01).Conclusion:After AMI ofRats, the expression of Rho kinase increased accompanied with the AI. Administration of Fasudil after AMI for 1 week could decreasemyocyte apoptosis by inhibit the Rho/Rock signaling pathway, and therefore protect the myocardia.