辛伐他汀抗高血压心肌纤维化与单核细胞趋化蛋白-1表达的关系

Effect of simvastatin on regression of pressure overload-induced rat's myocardial fibrosis and its relationship with monocyte chemoattractant protein-1

目的:研究辛伐他汀对腹主动脉缩窄性高血压大鼠心肌单核细胞趋化蛋白-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:应用腹主动脉缩窄法(AC)建立大鼠压力负荷模型,18只SD大鼠随机分为假手术组、手术组、辛伐他汀组,每组6只。4周后颈动脉插管测大鼠血压及计算左心室质量分数(LVW/BW),苦味酸-天狼猩红染色观察心肌间质胶原容积分数(CVF)和心肌血管周围胶原面积比(PVCA)反映心肌纤维化程度,免疫组化染色观察单核巨噬细胞抗原(ED1)数量,ELISA法和逆转录聚合酶链式反应(RT-PCR)分别检测辛伐他汀对心肌MCP-1蛋白和mRNA表达的影响。结果:手术组和辛伐他汀组大鼠平均动脉压(MBP)、LVW/BW、MCP-1蛋白和MCP-1 mRNA表达均显著高于假手术组(P<0.05或P<0.01),手术组CVF和PVCA、ED1阳性细胞数显著高于假手术组(P<0.01),但是辛伐他汀组与手术组MBP变化相近(P>0.05),辛伐他汀组较手术组LVW/BW、CVF和PVCA、ED1阳性细胞数、MCP-1蛋白和MCP-1 mRNA表达均显著降低(P<0.01)。结论:辛伐他汀可以抗心肌纤维化,其机制可能与降低MCP-1表达,减少巨噬细胞浸润有关。

ABSTRACT AIM： To study the effect of 3-hydroxy-3- methylglutaryl coenzyme A （HMG-CoA） reductase inhibitor simvastatin on MCP-1 expression and macrophages infiltration in pressure overload-induced myocardial fibrosis in rats with hypertension induced by abdominal aortic coarctation and further clarify the underlying mechanism of the treatment. METHODS： Pressure overload-induced rat model was established by abdominal aorta constriction （AC）. Eighteen SD rats were divided randomly into sham group, AC group and simvastatin group. At the ending of observation, mean arterial blood pressure （MBP） was measured by carotid artery intubation, and ratio of ventricle mass to body weigh （LVW/BW） was calculated. Myocardial interstitial fibrosis and perivascular fibrosis were evaluated by PAS. lmmunohistochemistry 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. RESUETS： MBP, LVW/BW, MCP-1 protein and mRNA expression in both AC group and simvastatin group were significantly higher than those in sham group （ P 〈 0.05 or P 〈 0.01 ）. Collagen perivascular circumferential volume fraction （CVF） and area （PCVA）, ED-1 positive cells in AC group were increased significantly compared with sham group （P 〈0.01）. LVW/BW, CVF, PCVA, ED-1 positive cells, MCP-1 protein and mRNA expression in simvastatin group were significantly lower than those in the AC group （ P 〈 0.01 ）. CONCLUSION： Simvastatin prevents pressure overload-induced rat＇s myocardial fibresis, which is associated with the reduction of MCP-1 in myocardium and interstitial macrophage infilration.