三磷酸腺苷敏感性钾通道Kir6.2 E23K多态性对大鼠心脏结构及功能的影响  

Effect of ATP sensitive potassium channel Kir6.2 E23K polymorphism on cardiac structure and function in rats

作　　者：冯颖[1] 万军[1] 袁文慧[1] 王梦龙[1] 刘梦林[1] 刘剑芳[1] 叶晶[1] 

机构地区：[1]武汉大学人民医院心内科武汉大学心血管病研究所心血管病湖北省重点实验室,湖北武汉430060

出　　处：《中国心脏起搏与心电生理杂志》2016年第3期249-252,共4页Chinese Journal of Cardiac Pacing and Electrophysiology

基　　金：国家自然科学基金(项目编号:81170208)

摘　　要：目的初步探讨在扩张型心肌病中E23K多态性对心脏结构及功能的影响。方法构建携带人心肌特异性启动子的α-MHC-Kir6．2KKDNA表达载体，运用显微注射法获得Kir6．2E23K多态性的大鼠模型（F0代），F0代大鼠与SD大鼠杂交，产出F1代大鼠并进行基因鉴定。将F1代雄性大鼠分为WT（WildType：不含有Kir6．2E23K多态性）组，E23K（含有Kir6．2E23K多态性）组，WT—DCM（wildType—Dilated Cardiomyopathy）组和E23K—DCM（E23K—Dilated Cardiomyopathy）组，每组10只。于8～12周时腹腔注射阿霉素构建扩张型心肌病（DCM）模型，对照组腹腔注射等量生理盐水。于模型构建完成后2周分别记录并分析4组大鼠心脏超声数据，并用天狼星红染色法检测其心肌胶原容积。结果成功构建携带人Kir6．2E23K多态性的载体α—MHC—KK并获得转基因大鼠。超声结果显示，经阿霉素诱导的大鼠（WT～DCM组和E23K—DCM组）与对照组（WT组和E23K组）相比心腔明显扩大，心功能显著降低，且E23K—DCM组大鼠较WT-DCM组大鼠心脏损伤更为明显（P〈0．05）；与WT—DCM组相比，E23K—DCM组大鼠心肌纤维化程度更为严重（P〈0．05）。结论在DCM中Kir6．2E23K多态性对大鼠心脏结构和功能均有显著影响。Objective To investigate the effect of E23K polymorphism on cardiac structrure and function in dilate cardiomyopathy. Methods Construction of a α-MHC-Kir6.2 KK DNA expression vector, which carried human cardiac specific promoter, and used the microinjection method to obtain the Kir6.2 E23K polymorphism in rat model （F0 generation）. F0 generation rats hybridized with SD rats, bred F1 generation rats and gene identification. The F1 generation male rats were divided into WT （wild type： does not contain Kit6.2 E23K polymorphism） group, E23K （containing Kir6.2 E23K poly- morphism） group, WT-DCM （wild type dilated cardiomyopathy） group and E23K-DCM （E23K-dilated cardiomyopathy） group, 10 rats in each group. At 8-12 weeks, intraperitoneal injection of Adriamycin constructed dilated cardiomyopathy （DCM） model, intraperitoneal injection of saline in control groups. Cardiac ultrasound data were recorded and analyzed in 2 weeks after the completion of the model construction, and the myocardial collagen volume was detected by Sirius red staining method. Results Successfully constructed the carrier of human Kir6. 2 E23K polymorphism gene. α- MHC-KK, transgenic rats were obtained. Ultrasound showed that the rats induced by Adriamycin （WT-DCM group and E23K-DCM group） compared to control group （WT group and E23K group）, heart cavity expanded significantly, heart function was meaningfully decreased, in addition, the heart injury in E23K-DCM group was more significant than that in the WT-DCM group （P〈0. 05）; pathological results suggested that the myocardial fibrosis in E23K-DCM group was more severe than that in the WT-DCM group （P〈0.05）. Conclusion The E23K Kir6.2 polymorphism has a significant impact on cardiac structure and function of rats in DCM. [Chinese Journal of Cardiac Pacing and Electrophysiology, 2016,30 （3） ： 249 - 252]

关 键 词：心血管疾病 Kir6.2亚基 E23K多态性 三磷酸腺苷敏感性钾通道 扩张型心肌病 

分 类 号：R331.38[医药卫生—人体生理学] R542.2[医药卫生—基础医学]