辛伐他汀抗心肌纤维化与单核细胞趋化蛋白-1表达的关系

EFFECT OF SIMVASTATIN ON RAT'S MYOCARDIAL FIBROSIS AND ITS RELATIONSHIP WITH MONOCYTE CHEMOATTRACTANT PRTEIN-1

目的研究辛伐他汀对盐酸异丙基肾上腺素(isoproterenol hydrochloride,Isp)所致心肌纤维化大鼠单核细胞趋化蛋白-1(MCP-1)表达及其巨噬细胞浸润的影响,探讨其抗纤维化的机制。方法应用注射Isp方法建立大鼠心肌缺血坏死模型,18只SD大鼠随机分为对照组、模型组和辛伐他汀组,每组6只。2周后Masson染色观察心肌间质胶原容积分数(CVF),免疫组化染色观察单核巨噬细胞抗原(ED1)数量,ELISA法和RT-PCR分别检测心肌MCP-1蛋白和mRNA的表达。结果模型组CVF、ED1阳性细胞数、MCP-1蛋白和MCP-1mRNA表达均高于对照组(P<0.01)。与模型组相比,辛伐他汀组CVF、ED1阳性细胞数、MCP-1蛋白和mRNA表达均降低(P<0.05或P<0.01),但仍高于对照组(P<0.05或P<0.01)。结论辛伐他汀可能通过降低MCP-1表达、减少巨噬细胞浸润发挥抗心肌纤维化作用。

Objective To study the effect of simvastatin on MCP- 1 expression and macrophages infiltration in myocardial fibrosis in rats and to further clarify the underlying mechanism of the treatment. Methods Isoproterenol hydrochloride was used to establish rats model. Eighteen SD rats were divided randomly into control group, model group and simvastatin group. Myocardial interstitial fibrosis was evaluated by Masson staining. Immunohistochemistry was used on myocardium for ED- 1 which was a marker of macrophage. MCP - 1 mRNA and protein expression levels in myocardium were determined with reverse transcription polymerase chain reaction （RT- PCR） and ELISA respectively. Results Collagen volume fraction （CVF）, PCVA, ED- 1 positive cells, MCP- 1 protein and mRNA expression in model group were significantly higher than those in the control group （P〈0.01）. Compared with model group, CVF, ED- 1 positive cells, MCP- 1 protein and mRNA expression were lower （P〈0.05 or P〈0.01）, but higher than control group （P〈0. 05 or P〈0. 01）. Conclusion Simvastatin prevents Ispinduced rat＇s myocardial fibrosis, which is associated with the reduction of MCP- 1 inmyocardium and interstitial macrophage infiltration.