瑞舒伐他汀对急性心肌梗死大鼠NF-κB和IL-6表达的影响

Effects of rosuvastatin on expressions of NF-κB and interleukin-6 in rats with acute myocardial infarction

目的:探讨瑞舒伐他汀(rosuvastatin,ROS)对大鼠急性心肌梗死(AMI)后心肌组织炎症的影响。方法:结扎20只雄性Wistar大鼠冠状动脉的左前降支(LAD)建立心梗模型。成功后,随机分为AMI组和ROS干预组,每组10只大鼠。另取10只大鼠作为假手术(Sham)组(仅穿线不结扎)。ROS干预组给予ROS 10 mg/(kg.d)灌胃;其他两组每只大鼠每天给予2 ml生理盐水灌胃。持续4周后,处死动物,取部分心肌非梗死边缘区组织做HE染色观察病理改变;其余心肌组织分别进行免疫组化染色及RT-PCR,检测NF-κB、IL-6及二者mRNA的表达。结果:心肌组织HE染色显示,与AMI组比较,ROS干预组心肌排列较整齐,心肌纤维断裂较少,心肌纤维样变减少,炎性细胞浸润减轻。Sham组NF-κB和IL-6均无明显表达。AMI组NF-κB和IL-6的mRNA和两种蛋白的表达均显著高于Sham组(P<0.05)。同AMI组相比较,ROS干预组NF-κB、IL-6 mRAN和两种蛋白的表达均显著下降(P<0.05),NF-κB和IL-6的表达呈正相关(r=0.85,0.75)。结论:ROS对AMI大鼠进行干预可调控NF-κB的活性,减少IL-6炎性因子的表达,可改善心肌重构。

AIM： To evaluate the effects of rosuvastatin on inflammation of myocardial tissues in rats with acute myocardial infarction （AMI）. METHODS： Twenty male Wistar rats with ligated LAD were used to establish models of AMI and the successfully established models were randomly divided into acute myocardial infarction group （AMI group） and rosuvastatin intervention group （ROS group）. Another 10 rats （sham group） were tested with pierced but not ligated LAD. Rats in ROS group were given rosuvastatin by gavage at 10 mg/（kg .day） dose levels, whereas rats in the other two groups were given 2 ml normal saline each day. Four weeks later, noninfarcted myocardial tissues were observed with HE section staining, whereas NF-κB and IL-6 were detected by immunohistochemistry and RT-PCR. RESULTS： HE section staining showed that cardiac tissues were diac tissue fiber, less fibrosis, and the inflammatory more orderly arrayed. There was less rupture of carcell reaction was milder in the ROS group compared with rats in the AMI group. No expressions of NF-κB and IL-6 were found in sham group. In AMI group, both mRNA expression and protein production of these cytokines were markedly higher than those in sham group （P 〈 0. 05）. Significant reductions of mRNA expression and protein production of NF-κB and IL-6 were observed in ROS group compared with those in AMI group （P 〈 0. 05 ）, NF-κB and IL-6 of the two were positively correlated （ r = 0.85,0.78 ）. CONCLUSION ： Rosuvastatin helps regulate the activation of NF-κB and reduces the expression of IL-6 in AMI rat; therefore, it is beneficial to the ventricular remodeling improvement.