厄贝沙坦对自发性高血压大鼠心肌Janus激酶-信号转导和转录活化因子信号通路的影响

目的 探讨厄贝沙坦对自发性高血压大鼠(SHR)心肌组织Janus激酶-信号转导蛋白和转录激活蛋白(JAK-STAT)信号转导通路及细胞凋亡的影响. 方法 30周龄WKY大鼠13只,设为WKY对照组;30周龄SHR 26只,随机分为SHR对照组和厄贝沙坦组.反转录-聚合酶链反应(RT-PCR)法检测血管紧张素Ⅱ1型(AT1)与2型(AT2)受体mRNA在心肌中的表达,免疫组化法检测心肌组织STAT1、STAT3表达,TUNEL细胞凋亡显色法进行细胞凋亡检测. 结果 (1)厄贝沙坦组与SHR对照组比较,AT1 mRNA表达水平显著降低(0.72±0.55对1.08±0.13,P<0.01),AT2 mRNA表达水平显著增高(0.30±0.32对0.25±0.35,P<0.01);(2)与SHR对照组比较,厄贝沙坦能降低STAT1表达(7.27±0.53对13.16±0.35,P<0.01),升高STAT3表达(5.41±0.37对4.82±0.34,P<0.01);(3)厄贝沙坦组心肌细胞凋亡率显著低于SHR对照组(P<0.01). 结论厄贝沙坦能调节心肌组织JAK-STAT信号转导通路,抑制细胞凋亡,从而发挥其心脏保护作用.

Effects of irbesartan on JAK-STAT signal transduction pathway in myocardium of spontaneous hypertensive rat

Objective To investigate the effects of irbesartan on regulating JAK-STAT signal pathway and apoptosis in myocardium of spontaneous hypertensive rat (SHR). Methods There were 13 Wistar-Kyoto (WKY) rats aged 30 weeks as WKY control group, and 26 SHRs at the same age were randomly divided into SHR control group and irbesartan treatment group (n=13, respectively). The mRNA expression levels of AT1 and AT2 were detected by RT-PCR. The STAT1 and STAT3 expression levels in myocardium were determined by immunohistochemical methods. The apoptosis rate of myocardial cells was measured by Colorimetric TUNEL. Results The mRNA expression level of AT1 was significantly lower in irbesartan group than in SHR control group (0.72±0.55 vs. 1.08±0. 13, P<0.01), while in study of irbesartan versus SHR control group, the mRNA expression level of AT2 was significantly higher (0.30±0.32 vs. 0.25±0.35, P<0.01), the STAT1 expression in protein level was significantly lower (7.27±0.53 vs. 13.16±0.35, P<0.01),and the STAT3 expression in protein level was significantly higher (5.41±0.37 vs. 4.82±0.34, P< 0.01). The apoptosis rate was significantly higher in SHR control group than in irbesartan group (P<0.01). Conclusions Irbesartan can regulate JAK-STAT signal transduction pathway in myocardium of SHR, and inhibit apoptosis of myocardium to produce a protective effect on the heart.