肺动脉高压大鼠肺小动脉内皮细胞间和右心室心肌中缝隙连接蛋白43表达变化的初步研究

摘要

目的:研究肺动脉高压大鼠及波生坦(bosentan)干预后肺小动脉内皮细胞间及右心室心肌中缝隙连接蛋白(Cx)43表达的变化,并探究其意义.方法:10只SD大鼠为正常对照组(n=10),不做任何处理;其余57只通过腹腔内注射野百合碱(60 mg/kg)两周后,随机将大鼠分成2组,肺动脉高压SD大鼠+安慰剂组(n＝35),肺动脉高压SD大鼠+波生坦组(n＝22),予以安慰剂或波生坦300 mg/(kg·d)治疗,每天一次,共计3周.通过免疫荧光的方法测定Cx43在肺小动脉内皮细胞间、右心室心肌组织中表达的变化.结果:在正常对照组的肺小动脉内皮细胞间未检测到Cx43,但在肺动脉高压SD大鼠+安慰剂组中肺小动脉内皮细胞间出现了Cx43的异常表达,肺动脉高压SD大鼠+波生坦组Cx43的表达水平显著下降,三组之间两两比较差异均有统计学意义(P<0.01).在右心室心肌纵切面,正常对照组的Cx43多数集中于与心肌细胞长轴垂直的端端连接处,少数位于与长轴平行的细胞侧侧连接处;而在肺动脉高压SD大鼠+安慰剂组Cx43的表达在端端连接处明显减少,在侧侧连接处明显增加;肺动脉高压SD大鼠+波生坦组Cx43的表达与正常对照组相似.三组单位面积的右心室心肌组织Cx43的表达面积的半定量分析差异无统计学意义(P>0.05).结论:肺小动脉内皮细胞间Cx43的异常表达在肺动脉高压的发病机制中可能起着非常重要的作用.右心室心肌Cx43的分布紊乱可能是导致右心室重塑的机制之一.%Objective To study the effect of bosentan for connexM3 ( Cx43) expression in endothelial cells of smail pulnonary artery and inmyocytes of right ventricle ( RV) h ratswith pulnonary arterial hypertension ( PAH).Methods:PAH rats' modelwas created bymonociotaline(60 mg1 kg) injection for2 weeks, then PHA rats were divided in two groups, PAH+ vehicle group (n = 35) , and PAH+ bosentan group(n = 22) , in which the rats received bosentan300 mg/( kg-day) for3 weeks In additbn,10 nomal rats were set as Control group C$3 expression in snail pulnonary artery endothelial cells and h RV myocytes were examined by inmuno fluorescence assayResults: For snail pulnonary artery, there was noC43 expression detected in endothelial cells in Control group, while it was found in both PAH+ vehicle group and in PAH bosentan group, and Qg> expression was significantly lower in PAH + bosentan group than that inPAH+ vehicle group, P<0. 01. ForRV myocytes, h Control group, most of C$3 staining was aggregated at the cell teminj, the stainingwas weak at the side to side cell junctbns; while inPAH+ vehicle group, Cx43 expressbnwas decreased at the cell temhi and increased at the side to sHe area; inPAH+ bosentan group, C;43 expressbnwas smilar to Control groupConclusion: InPAH rats, the abnomal expression of Cx43 in snail pulnonary artery endothelial cellsmight be associated with PAH occurrence Perturbation of C;43 h RV myocytes could be one of the reasons for RV remodel