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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-Kir6.2KK DNA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(Wild Type:不含有Kir6.2E23K多态性)组,E23K(含有Kir6.2E23K多态性)组,WT-DCM(Wild Type-Dilated Cardiomyopathy)组和E23KDCM(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 structure and function in dilated cardiomyopathy. Methods The α-MHC-Kir6.2KK DNA vector carrying human cardiac muscle-specific promoter was constructed. The Kir6.2E23K polymorphism rat model (F0) was obtained by microinjection. The F0 rats and SD rats F1 hybrids were produced and genetically identified. F1 male rats were divided into WT (Wild Type: Kir6.2E23K polymorphism) group, E23K (Kir6.2E23K polymorphism) group, WT-DCM (Wild Type-Dilated Cardiomyopathy) group, and E23KDCM E23K-Dilated Cardiomyopathy group, 10 in each. Adriamycin was intraperitoneally injected at 8-12 weeks to establish a model of dilated cardiomyopathy (DCM). The control group was injected intraperitoneally with normal saline. Two weeks after the completion of the model construction, the cardiac ultrasound data of four groups were recorded and analyzed respectively. The myocardial collagen volume was measured by Sirius red staining. Results The vector α-MHC-KK carrying human Kir6.2E23K polymorphism was successfully constructed and the transgenic rats were obtained. Ultrasound results showed that the cardiac cavity was significantly enlarged and the cardiac function was significantly decreased in doxorubicin-induced rats (WT-DCM group and E23K-DCM group) compared with the control group (WT group and E23K group) Compared with WT-DCM group, the degree of myocardial fibrosis in E23K-DCM group was more severe (P <0.05). Conclusion Kir6.2E23K polymorphism in DCM significantly affects the cardiac structure and function in rats.