DSG2^(F536C)点突变基因敲入小鼠的心外膜电压标测与心肌纤维化  

The study of occurrence of epicardial voltage mapping and cardiac fibrosis in DSG2 knock-in mice

作　　者：纪佳妹 郭萍 王学成 吴奕章 杨稳[1] 周秀娟[1] 杨兵[1] JI Jia-mei;GUO Ping;WANG Xue-cheng;WU Yi-zhang;YANG Wen;ZHOU Xiu-juan;YANG Bing(Department of Cardiology,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,Jiangsu,China;Department of Cardiology,Shanghai East Hospitals Tongji University,Shanghai 200120,China)

机构地区：[1]南京医科大学第一附属医院心血管内科,江苏南京210029 [2]同济大学附属上海东方医院心血管内科,上海200120

出　　处：《中国心脏起搏与心电生理杂志》2021年第4期347-350,共4页Chinese Journal of Cardiac Pacing and Electrophysiology

摘　　要：目的探讨桥粒芯糖蛋白2(DSG2)点突变(DSG2^(F536C))小鼠心外膜电压标测及心肌纤维化特征.方法通过点突变基因敲入建立DSG2^(F536C)小鼠模型,根据基因型分为纯合子组(Hom)、杂合子组(Het)和野生型组(WT),每组各6只.以10周龄小鼠,采用多微电极紧贴在小鼠左、右室表面行在体心外膜标测,Matlab软件分析心外膜标测数据,测定左、右室单极与双极电压的最高值.取心肌标本,Masson三色染色后光镜观察心脏形态变化,并测量左、右室胶原容积分数,评估心肌纤维化.结果Hom组的右室单极电压最高值较WT组、Het组小鼠显著降低[(0.582±0.080)mV vs(2.217±0.146)mV、(2.017±0.062)mV,P<0.05],右室双极电压最高值较W T组显著降低[(0.210±0.080mVvs0.978±0.190mV,P<0.05].三组左室单极与双极电压最高值无差异[WT:(2.340±0.560)mV、Het:(1.920±0.190)mV、Hom:(1.975±0.180)mV,P>0.05;WT:(2.083±0.620)mV、Het:(1.610±0.200)mV、Hom:(1.317±0.120)mV,P>0.05].与WT组、Het组相比,Hom组右室胶原容积积分显著升高(39.792%±9.322%vs 3.161%±0.296%、3.157%±0.213%,P<0.001),左室则无显著差异.Hom组已有显著心肌纤维化形成,而WT组、Het组则无相似表现.结论DSG2^(F536C)点突变基因敲入纯合子小鼠在10周龄时右室心外膜单、双极电压均明显降低,心肌纤维化程度显著.左室纤维化不明显,相应电压标测也未测得显著差异.Objective To observe the variation of epicardial mapping voltage, so as to help determine cardiac fibrosis. Methods DSG2F536 C knock-in mice were generated through homologous recombination of target gene knock-in strategy. DSG2F536 C knock-in mice with three genotypes were generated, including wild type mice(WT) group, heterozygous mice(Het) group, homozygous mice(Hom) group. 10-week-old mice were divided into three groups of six mice each. Firstly, we recorded the epicardial unipolar and bipolar voltage by epicardial mapping. Then the pathological characteristics of the myocardium were assessed by Masson trichrome staining. Results The right ventricle unipolar voltage of Hom group was significantly lower than that in WT group and Het group among 10 weeks mice[(0.582±0.08) mV vs(2.217±0.146) mV,(2.017±0.062) mV,P<0.05]. The right ventricle bipolar voltage of Hom were lower than the WT group among 10 weeks mice [(0.210±0.080) mV vs(0.978±0.190) mV,P<0.05]. There was no significant difference found among the left ventricle unipolar and bipolar voltage of three groups among 10 weeks mice [WT:(2.340±0.560) mV, Het:(1.920±0.190) mV, Hom:(1.975±0.180) mV, P>0.05;WT:(2.083±0.620) mV, Het:(1.610±0.200) mV, Hom:(1.317±0.120) mV, P>0.05]. Compared with WT group and Het group,the collagen volume integral of Hom group was significantly higher(39.792% ±9.322% vs 3.161% ±0.296%,3.157% ±0.213%,P <0.001).However,there was no significant difference found in the left ventricle collagen volume fraction of three groups among 10 weeks mice.Furthermore,Masson staining results showed enlargement,thinning,and fibrosis of the right ventricle in the Hom group mice. Conclusions DSG2F536 Cknock-in homozygous mice shows significant decrease in unipolar and bipolar right ventricular voltages at 10 weeks and demonstrated the formation of right ventricular fibrosis,which indicates that myocardial fibrosis can be evaluated by epicardial voltage change.[Chinese Journal of Cardiac Pacing and Electrophysiology,2021,35(4):347-350]

关 键 词：心血管病学 致心律失常性右室心肌病 桥粒芯糖蛋白2 基因敲入小鼠 心外膜电压标测 心肌纤维化 

分 类 号：R541.7[医药卫生—心血管疾病] R542.2[医药卫生—内科学]