血管紧张素Ⅲ受体AT1R、AT2R和ERK1在大鼠主动脉损伤中的表达及其意义

目的探讨大鼠主动脉损伤后血管紧张素受体（AT1R、AT2R）和胞外信号调控激酶1（ERK1）表达及其意义。方法 36只SD大鼠随机分为正常组、单纯损伤组、PD123319（AT2R拮抗剂）组、缬沙坦（AT1R拮抗剂）组、PD98059（ERK1拮抗剂）组、缬沙坦＋PD98059组,其中后4组在主动脉球囊损伤模型制作前、后给予相应的受体拮抗剂。造模后7d处死,用RT-PCR和Western blotting检测降主动脉中层及内膜中AT1R、AT2R和ERK1表达。结果单纯损伤组、PD123319组和PD98059组AT1R表达明显高于正常组、缬沙坦组和缬沙坦＋PD98059组（P〈0.01）。PD123319组AT2R表达明显高于其它4组（P〈0.01）。与单纯损伤组比较,缬沙坦组、PD98059组及缬沙坦＋PD98059组ERK1表达明显下调（P〈0.01）。结论 AT2R可能通过下调AT1R激活的ERK1来抑制新生内膜形成,AT2R可望成为治疗血管成形术后再狭窄的新靶点。

Expression of angiotensin II receptors AT1R and AT2R and ERK 1 and its significance in rats with aortal injury

Objective To study the expression of angiotensin Ⅱ receptors AT1R and AT2R and extracellular regulated kinase 1（ERK1） after aortal injury and its significance in rats.Methods Thirty-six rats were randomly divided into 6 groups,e.g.,normal,simple injury,PD123319（AT2R antagonist）,valsartan（AT1R antagonist）,PD98059（ERK1 antagonist） and valsartan＋PD98059 groups,and the latter 4 groups were treated with various receptor antagonists before and after establishment of balloon-injured aorta model.All rats were sacrificed 7 days after aortal injury,and expression of AT1R,AT2R and ERK1 was determined by RT-PCR and Western blotting in the middle layer and intima of aorta.Results AT1R expression in simple injury,PD123319 and PD98059 groups was significantly higher than that in normal,valsartan and valsartan ＋ PD98059 groups（P0.01）. AT2R expression in PD123319 group was superior to that in other 4 groups（P0.01）.ERK1 expression was downregulated in valsartan,PD98059 and valsartan ＋ PD98059 groups compared with simple injury group（P0.01）.Conclusion AT2R could inhibit the neointimal hyperplasia by downregulation of AT1R-activated ERK1,and would become a novel target for restenosis treatment of postangioplasty.