Sheng Fu-qiang, Xu Rong, Cheng Long-xian, Zeng Qiu-tang, Gao Wen, Wang Wei, Dang Shu-yi, Wang Chong-quan, He Chao-rong
Department of Cardiology, Affiliated Taihe Hospital, Yunyang Medical College, Shiyan, Hubei.
Acta Cardiol. 2009 Dec;64(6):779-85. doi: 10.2143/AC.64.6.2044743.
The objective of this study was to investigate the effect of simvastatin on TLR4,TNF-alpha and IL-6 expression in the myocardium and its relation to left ventricular (LV) remodelling in a rat model of myocardial infarction (MI) and to investigate the mechanism by which simvastatin improves LV remodelling in rats after MI.
The rat MI models were established by ligation of the left anterior descending coronary artery and divided into three groups: (I) an untreated MI group; (2) a group treated with simvastatin [40 mg/(kg/d)] for 4 weeks; (3) the sham group. Cardiac geometry and function were determined by echocardiography and infarct size was determined by the histomorphometric analysis; the expression ofTLR4 in the myocardium was measured by RT-PCR and western blotting;TNF-alpha and IL-6 levels in myocardial homogenate and serum were measured by ELISA. LVEDD and LVESD significantly increased and fractional shortening (FS) markedly decreased in the MI group. It was clear that simvastatin inhibited LV dilation and improved LV function after MI without affecting infarct size. The expression of TLR4, TNF-alpha and IL-6 in the myocardium significantly increased in the MI group and simvastatin markedly inhibits the expression of TLR4, TNF-alpha, and IL-6 in the myocardium after MI. Serum TNF-alpha and IL-6 levels between the MI group and the simvastatin group remained unchanged. Both in the MI group and the simvastatin group,TLR4 protein positively related to LVEDD and to the levels of TNF-alpha and IL-6 in the myocardium, respectively.
Amelioration of LV remodelling in rats after MI by simvastatin might be associated with its effect on the TLR4-mediated signalling pathway in the myocardium.
本研究旨在探讨辛伐他汀对心肌梗死（MI）大鼠模型心肌中Toll样受体4（TLR4）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）表达的影响及其与左心室（LV）重构的关系，并研究辛伐他汀改善MI后大鼠LV重构的机制。
通过结扎左冠状动脉前降支建立大鼠MI模型，并分为三组：（I）未治疗的MI组；（2）辛伐他汀[40mg/（kg/d）]治疗4周的组；（3）假手术组。通过超声心动图测定心脏几何形状和功能，通过组织形态计量分析确定梗死面积；通过逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法测定心肌中TLR4的表达；通过酶联免疫吸附测定（ELISA）法测定心肌匀浆和血清中TNF-α和IL-6的水平。MI组左心室舒张末期内径（LVEDD）和左心室收缩末期内径（LVESD）显著增加，而短轴缩短率（FS）明显降低。显然，辛伐他汀可抑制MI后LV扩张并改善LV功能，但不影响梗死面积。MI组心肌中TLR4、TNF-α和IL-6的表达显著增加，而辛伐他汀可显著抑制MI后心肌中TLR4、TNF-α和IL-6的表达。MI组和辛伐他汀组之间血清TNF-α和IL-6水平保持不变。在MI组和辛伐他汀组中，TLR4蛋白分别与LVEDD以及心肌中TNF-α和IL-6的水平呈正相关。
辛伐他汀改善MI后大鼠LV重构可能与其对心肌中TLR4介导的信号通路的作用有关。
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