TRPM7抑制剂对压力超负荷大鼠心肌肥厚的影响  

Effect of TRPM7 inhibitor on pressure overload induced cardiac hypertrophy

作　　者：李燕[1] 江慧[2] 阮承超[1] 钟久昌[1] 高平进[1] 朱鼎良[1] 郭淑杰[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院上海市高血压研究所,上海200025 [2]中国科学院上海生命科学研究院健康科学研究所,上海200025

出　　处：《中国分子心脏病学杂志》2013年第2期501-504,共4页Molecular Cardiology of China

基　　金：上海交通大学医学院校基金(11XJ21034)

摘　　要：目的研究瞬时受体电位通道M7(Transient receptor potential melastatin 7 channels,TRPM7)抑制剂对压力超负荷所致心肌肥厚及炎症反应的影响。方法雄性SD大鼠20只,随机分为三组:假手术组(n=6)、主动脉缩窄组(TAC组)(n=7)、TAC+2-Aminoethoxydiphenyl Borate(2-APB)组(TRPM7抑制剂组)(n=7)。通过在右侧无名动脉和左侧颈总动脉之间缩窄胸主动脉而诱导大鼠心肌肥厚模型。抑制剂组造模前一天开始给药,腹腔注射,每3天一次,2.5mg/kg。造模2周后取各组大鼠左心室,将心肌样本切片,苏木素-伊红染色观察心肌形态学改变;Masson染色检测心肌组织胶原沉积,免疫荧光检测TRPM7、巨噬细胞标记分子CD68和单核细胞趋化蛋白-1(MCP-1)的表达。结果 TAC组与假手术组相比,心肌细胞直径增大,胶原沉积增多,TRPM7、CD68、MCP-1表达均增加;TRPM7抑制剂处理后,上述情况均有改善。结论 TRPM7的表达在压力超负荷诱导的心肌肥厚模型中显著增加,抑制TRPM7改善心肌肥厚,减少心肌组织胶原沉积及巨噬细胞浸润。Objective To investigate the effects of Transient receptor potential melastatin 7 channels （TRPM7） inhibitor on the hypertrophic myocardium and inflammation induced by pressure overloaded in rats. Methods Twenty male Sprague Dawley （SD） rats were randomly divided into three groups： sham-operated group （ n = 6 ）, transverse aortic constriction （TAC） group（ n = 7 ）, TAC and 2-Aminoethoxydiphenyl Borateinduce （2- APB） group （TRPM7 inhibitor group） （ n = 7 ）. The models of cardiac hypertrophy were established in vivo, and the thoracic aorta was partially tied between the right innominate arties and the left common carotid arteries.Sham surgery, in which a suture was passed around the aorta but removed without tying was performed as a control. Inhibitor group witnessed the day before starting drug, intraperitoneal injection, once every 3 days, 2.5rag/ kg. After treatment for 2 weeks, Left ventricular （LV） myocardial samples were obtained for histological examination, Masson staining was used to detect the deposition of collagen, and immunofluorescence was used to detect the expression of TRPM7, CD68 （biomarker of macrophages） and monocyte chemotactic protein-1 （MCP-I）. Results After 2 weeks, the diameter of cardiomyocytes, collagen deposition, and expression of TRPM7, CD68 and MCP-1 were significantly increased in TAC group as compared with sham-operated group. The relative parameters in inhibitor group were reduced as compared with TAC group. Conclusion The expression of TRPM7 was significantly increased in the hypertrophic myocardium induced by pressure overload. Inhibition of TRPM7 could reduce cardiac hypertrophy, collagen deposition and macrophage infiltration.

关 键 词：TRPM7 心肌肥厚 主动脉缩窄 巨噬细胞 

分 类 号：R542.2[医药卫生—心血管疾病]