辛伐他丁减少Connexin43表达及兔粥样硬化斑块形成.docVIP

辛伐他丁减少Connexin43表达及兔粥样硬化斑块形成 　　　作者：李建军，林宏，李柱一，李宏增 【关键词】 动脉粥样硬化 Simvastatin reduces Connexin43 expression and inhibits rabbit atherosclerotic lesion formation 　　【Abstract】 AIM: To demonstrate that simvastatin can influence atherosclerotic plaque formation and stability by decreasing the expression of gap junction protein connexin43 (Cx43) in atherosclerotic lesions. METHODS: The role of Cx43 in atherogenesis was examined by a pharmacological approach. The rabbit model of atherogenesis was established by a highcholesterol diet. The expression of connexin 43 and macrophages in vivo was determined by immunohistochemistry and the expression of connexin 43 in cultured smooth muscle cells was determined with Western blot. The quantity of connexin43 expression was analyzed with computer images. RESULTS: We observed that HMGCoA reductase inhibitors, or “statins”, lipidlowering drugs well known for their pleiotropic antiatherogenic effects, reduced Cx43 expression in primary human vascular cells in vitro. Atheroma of rabbits orally treated with simvastatin contained fewer inflammatory cells and exhibited thicker fibrous caps than controls, which was associated with reduced Cx43 expression in lesions of statintreated rabbits. CONCLUSION: These data indicate the critical role of Cx43mediated gap junctional communication in atherosclerotic plaque formation. Reduced Cx43mediated intercellular communication leads to changes in atherogenesis. These findings show that Cx43mediated intercellular communication can be used as a new potential therapeutic target in atherogenesis. 　　【Keywords】 atherosclerosis; simvastatin; Connexin43 　　【摘要】 目的：证明辛伐他丁可以通过减少缝隙连接蛋白43（Connexin43, Cx43）的表达影响粥样斑块的形成及稳定性. 方法：高脂饲料喂养建立粥样硬化模型，治疗组给予辛伐他丁口服，活体内的Cx43和巨嗜细胞检测使用免疫组织化学方法，培养平滑肌细胞的Cx43检测使用免疫印记方法，Cx43的半定量使用计算机图像处理. 结果：药物干预的培养细胞和模型治疗组中Cx43的表达均明显减少，斑块的组成中，炎症细胞减少50％，胶原纤维平滑肌细胞含量增加. 结论： Cx43介导的细胞间通讯在粥样硬化形成中起重要作用，同时辛伐他丁减少Cx43的表达可以增加斑块的稳定性，Cx43成为动脉粥样硬化治疗中一个新的治疗靶点. 　　【关键词】 动脉粥样硬化；辛伐他丁；连接蛋白43 　 　　0引言 　　动脉粥样硬化主要是一种免疫炎