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目的研究高血压大鼠胸主动脉以及周期性张应变刺激下血管平滑肌细胞(VSMCs)的Rho蛋白解离抑制因子(RhoGDIα)的表达变化,探讨血管紧张素Ⅱ(AngⅡ)信号通路对其表达的调控影响。方法应用实时PCR和Western blotting技术分别检测4周、12周和18周自发性高血压大鼠(SHR,n=4)和正常血压京都种鼠(WKY,n=4)胸主动脉RhoGDIαmRNA和蛋白的表达;免疫组织化学检测RhoGDIα在SHR和WKY胸主动脉的定位;Westernblotting技术检测腹主动脉缩窄性高血压大鼠(ACR,n=6)胸主动脉RhoGDIα蛋白的表达;应用细胞应变加载系统对大鼠胸主动脉VSMCs施加1Hz、10%的周期性张应变,在有或无血管紧张素亚型Ⅰ(AT1)受体拮抗剂L-158809的条件下观察周期性张应变刺激对VSMCs RhoGDIα蛋白表达的影响。结果4周与12周SHR和WKY胸主动脉RhoGDIα表达无显著性差异,而在18周组,SHR胸主动脉RhoGDIα表达显著高于WKY。RhoGDIα主要存在于血管中膜VSMCs。2周和4周ACR胸主动脉RhoGDIα表达较正常对照组显著上调,提示在高血压状态下的主动脉RhoGDIα的表达上调。10%周期性张应变加载抑制了VSMCs的RhoGDIα表达,加入ATI受体拮抗剂后RhoGDIα表达显著低于10%周期性张应变加载组。结论大鼠高血压时主动脉RhoGDIα表达上调;AngⅡ信号通路在RhoGDIα表达调控中起重要作用。
Objective To investigate the expression of RhoGDIα in the thoracic aorta and vascular smooth muscle cells (VSMCs) induced by cyclic tensile stress in rats, and to investigate the effect of angiotensin Ⅱ (AngⅡ) signaling pathway on the expression of RhoGDIα Regulate the impact. Methods Real-time PCR and Western blotting were used to detect the expression of RhoGDIαmRNA and protein in thoracic aorta of spontaneously hypertensive rats (SHR, n = 4) and normotensive Kyoto rats (WKY, n = 4) The expression of RhoGDIα in thoracic aorta of abdominal aorta constriction hypertensive rats (ACR, n = 6) was detected by Western blotting. The rats were subjected to cyclical tensile strain of 1 Hz and 10% at a time of 1 Hz. The effects of cyclic tensile stress on the proliferation of VSMCs (VSMCs) were observed in the presence or absence of angiotensin Ⅰ receptor antagonist L-158809 Effect of RhoGDIα protein expression. Results There was no significant difference in the expression of RhoGDIα in SHR and WKY thoracic aorta at 4 weeks and 12 weeks. However, in 18 weeks, the expression of RhoGDIα in SHR was significantly higher than that in WKY. RhoGDIα is mainly found in vascular mesangial VSMCs. The expression of RhoGDIα in ACR thoracic aorta was significantly upregulated at 2 weeks and 4 weeks, suggesting that the expression of RhoGDIα in the aorta of hypertensive rats was up-regulated. The 10% cyclic tensile strain inhibited RhoGDIα expression in VSMCs, and the expression of RhoGDIα was significantly lower than that in 10% cyclic strain loaded with ATI receptor antagonist. Conclusion The expression of RhoGDIα in aorta of rats with hypertension is up-regulated. AngⅡ signaling pathway plays an important role in the regulation of RhoGDIα expression.