大鼠急性心肌梗死后心脏炎症细胞因子基因和蛋白表达及辛伐他汀干预研究

Expression of inflammatory cytokines in rat hearts after acute myocardial infarction and effect of simvastatin

目的探讨辛伐他汀对急性心肌梗死(AMI)后大鼠心脏炎症细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和白细胞介素-10(IL-10)mRNA表达和蛋白质产生的影响。方法Wistar大鼠36只分3组:(1)假手术(Sham)组;(2)心肌梗死对照(MI-C)组;(3)辛伐他汀(MI-S)组。动物笼养4周取出心脏,沿乳头肌等分为二,一半用逆转录聚合酶链反应法测定心脏细胞因子mRNA表达,另一半用Western blot测定细胞因子蛋白质生成量。结果Sham组上述细胞因子均无明显表达,MI-C组TNF-α,IL-1β,IL-6和IL-10 mRNA和蛋白产生均显著高于Sham组;同MI-C组比较,MI-S组的TNF-α,IL-1β,IL-6 mRNA和蛋白生成均显著下降,而IL-10的mRNA和蛋白明显升高。结论辛伐他汀明显降低AMI后大鼠心脏的致炎症细胞因子,而升高炎症保护因子IL-10。

Objectives To study the effect of simvastatin on mRNA expression and protein production of inflammatory cytokines, including TNF-α, IL-1β, IL-6 and IL-10, in rat hearts after acute myocardial infarction （MI） .Methods The rats were divided into three groups： ①Sham group（Sham） ： the left descending coronatry arteries （LADs） of rats were not ligated; ②MI control group （MI-C） ： the LADs were ligated; ③Simvastatin group （MI-S） ： LADs were ligated and gavage with simvastatin 40 mg/kg per day was given. All animals were caged to feed for 4 weeks. At the fourth week, the rats were sacrificed and their hearts were taken and cut into two equal parts ： one was used to determine mRNA expression of cardiac cytokines by RT-PCR and another was used to measure protein production of cytokines by Western blot. Results No expression of all inflammatory cytokines mentioned above was found in Sham group. In the MI-C group, both mRNA expression and protein production of these cytokines markedly increased （ P 〈 0.01 ）. Compared with MI-C group, the MI-S group displayed significant reduction of mRNA expression and protein production of TNF-α, IL-1β and IL-6, and marked increase in IL-10 mRNA expression and protein production （ P 〈 0.01）. Conclusion Simvastatin markedly reduced pro-inflammatory cytokines, and increased inflammation-preventing cytokine. The mechanism needs to be elucidated.