孕鼠肝内胆汁淤积症:胎鼠心肌细胞缝隙连接蛋白Cx43、Cx45表达及意义

Expression of myocardium connexin-43 and connexin45 and sudden death in fetal rat of intrahepatic cholestasis of pregnancy

目的:探讨肝内胆汁淤积症(ICP)孕鼠的胎鼠心肌细胞缝隙连接蛋白43(Cx43)和缝隙连接蛋白45(Cx45)的表达。方法:应用雌、孕激素建立妊娠肝内胆汁淤积大鼠模型,透射电镜观察胎鼠心肌细胞闰盘超微结构,免疫组化、RT-PCR和Western Blot检测胎鼠心肌细胞Cx43和Cx45的表达。结果:(1)ICP组胎鼠心肌细胞闰盘结构部分模糊,缝隙连接消失;(2)免疫组化、RT-PCR和Western blot实验均发现,ICP组胎鼠心肌细胞Cx43蛋白表达显著下调,与正常组胎鼠比较,差异有极显著性,均P<0.01。(3)免疫组化、RT-PCR和Western blot实验均发现,ICP组胎鼠心肌细胞Cx45蛋白表达与正常组胎鼠比较差异无显著性,P>0.05。结论:ICP孕鼠的胎鼠心肌细胞缝隙连接超微结构发生改变,Cx43蛋白表达下调,缝隙连接通讯受到明显抑制,可能导致胎鼠发生心律失常和猝死。

Objective：To investigate the expression of myoeardium connexin43 and connexin45 in fetal rat of intrahepatic eholestasis of pregnancy（ICP）. Methods：The animal model of ICP was induced by 17- α- Ethinylestradiol and Progesterone. Ultrastruettmal changes of intercalated disk of fetal rat myocardial cells （FRMCs） were observed by electromicroscope.Expression of connexin43 and connexin45 of FRMCs were observed by immunohistocbemistry, RT- PCR and Western Blot. Results： （ 1 ） It showed vague ultrastmcture in some parts of intercalated disk and disappeared gap junctions of FRMCs in Group ICP. （2} Expression of connexin43 by immunohistochemistry, RT- PCR and Western Blot was downregulated significantly in FRMCs of Group ICP when compared to control,P 〈0.01. （3） No obvious differences were found about the expression of counexin45 by immunohistochemistry, RT - PCR and Western Blot in FRMCs between Group ICP and control, P 〉 0.05. Conclusion： It demonstrated that uhrastmctural changes of gap junction, downregulatinn of connexin43 and inhibition of gap junction intercellular communication in FRMCs might contribute to fetal rat arrhythmia and sudden death in ICP.