文档介绍:AT2对成年压力超负荷性肥大心肌细胞TNFα、IL1β及IL6分泌的调控
(作者:___________单位: ___________邮编: ___________)
作者:周娟,徐心,刘进军,林元喜,高广道
【摘要】目的观察AT2对肥大心肌细胞炎症因子合成的调控作用及AT1和AT2间的相互关系。方法采用腹主动脉缩窄法构建SD大鼠压力超负荷性心肌肥大模型。选用术后8周肥大的心肌细胞,将其分为AngⅡ组、AngⅡ+losartan组、AngⅡ+PD123319及AngⅡ+losartan+PD123319组。待实验结束,RTPCR法检测细胞TNFα、IL1β及IL6的mRNA表达水平,放免法检测TNFα、IL1β及IL6的蛋白表达。结果与AngⅡ组相比,AT1拮抗剂losartan不影响TNFα和IL1β的mRNA及蛋白表达。单独应用AT2拮抗剂PD123319及联合应用losartan和PD123319均可使TNFα和IL1β的mRNA及蛋白表达水平下调。联合应用二者TNFα和IL1β mRNA的表达水平介于单独应用losartan和PD123319组之间。与AngⅡ单独联用losartan或PD123319相比,同时联用二者可使IL6 mRNA的表达水平上调。结论 AT2参与了肥大心肌细胞炎症因子的表达调控。AT1与AT2之间并非简单的拮抗关系。
【关键词】心肌细胞;血管紧张素
Ⅱ二型受体;肿瘤坏死因子α;白介素1β;白介素6
ABSTRACT: Objective To investigate the role of AT2 in inflammatory factor synthesis of adult hypertrophic cardiomyocytes induced by pressure overload and the relationship between AT1 and AT2. Methods The left ventricular hypertrophy induced by pressure overload was achieved by placing a band around the abdominal aorta. We isolated and purified hypertrophic cardiomyocytes at 8 weeks after operation. The cardiomyocytes were randomly divided into 4 groups: AngⅡ, AngⅡ+losartan, AngⅡ+PD123319 and AngⅡ+losartan+PD123319 groups. The mRNA levels of TNFα, IL1β and IL6 were detected by RTPCR and the protein expression of TNFα, IL1β and IL6 in medium were detected by radioimmunoassay. pared with that of the AngⅡgroup, losartan could not influence the mRNA and protein expression of TNFα and IL1β, but PD123319 decreased them severely. The mRNA and protein expression of TNFα and IL1β also decreased with losartan and PD123319 treatment, but they were higher than in PD123319 alone treatment group. Compared with the AngⅡ, AngⅡ+losartan and AngⅡ+PD123319 groups, the IL6 mRNA increased when cells were treated with losartan and PD123319 simultaneously. Conclusion AT2 can regulate the expression of inflammatory
factors of hypertrophic cardiomyocytes. The relationship between AT1 and AT2 is not only antagonistic.
KEY WORDS: cardiomyocyte; ang