血管紧张素Ⅱ通过下调血管外膜过氧化氢酶促进血管重塑的研究

Angiotensin Ⅱ promotes vascular remodeling by down-regulation of adventitia catalase

目的 探讨血管紧张素Ⅱ（AngiotensinⅡ,AngⅡ）是否通过调控血管外膜过氧化氢酶（Catalase,CAT）促进血管重塑.方法 培养大鼠胸主动脉外膜成纤维细胞,分为对照组、AngⅡ组、PD98059（ERK1/2抑制剂）组、AngⅡ＋PD98059组,取4～7代用于实验;使用含107mol/L Ang Ⅱ的DMEM培养液分别刺激成纤维细胞0、0 5、2、6、12、24h,研究Ang Ⅱ对CAT作用的时间关系;分别以0、10^8、10^7、10^6、10^5mol/L的AngⅡ刺激成纤维细胞24h,研究Ang Ⅱ对CAT作用的浓度关系;采用PD98059（ERK1/2抑制剂）,研究ERK1/2信号通路对CAT表达的影响.结果 AngⅡ能够显著下调CAT的表达,并呈时间和剂量依赖性;AngⅡ能够通过ERK1/2信号通路下调血管外膜CAT的表达,阻断ERK1/2信号通路能够恢复CAT的表达.结论 AngⅡ可能通过ERK1/2信号通路下调血管外膜CAT的表达,进而促进血管重塑的发生,导致血管病理性重塑发生.

Objective To investigate the effect of ANG Ⅱ on vascular remodeling and its relation to regulation of adventitia catalase.Methods Adventitia fibroblasts were collected from rat thoracic aorta.The cultured adventitia fibroblasts were treated with ANG Ⅱ,PD 98059 （ERK1/2 inhibitor） or ANG Ⅱ with PD98059,respectively.Fibroblasts were treated with 107mol/L ANG Ⅱ for 0,0.5,2,6 and 24h; or with 0,10^8,10^7,10^6,10^5mol/L ANG Ⅱ for 24h.The catalase（CAT） contents in culture supernatants were measured.Results ANG Ⅱ remarkably decreased CAT contents in a time-dose dependent manner.Blockage of ERK1/2 signal pathway by PD98059 increased the expression of CAT in adventitial fibroblasts.Conclusion ANG Ⅱ can down-regulate the adventitia CAT through ERK1/2 signal pathway,which leads to the vascular remodeling.