缬沙坦对大鼠主动脉内皮球囊损伤后血管紧张素转换酶2表达的影响及其机制  

Effects of valsartan on aortic angiotensin converting enzyme 2 expression after aortic balloon injury in rats

作　　者：李永红[1] 安毅[1] 王其新[1] 苘瑜林[1] 刘平[1] 任贝贝[1] 

机构地区：[1]青岛大学医学院附属医院心内科,266003

出　　处：《中华心血管病杂志》2012年第8期697-701,共5页Chinese Journal of Cardiology

基　　金：国家自然基金面上项目（81071246）

摘　　要：目的研究血管内皮球囊损伤后血管内膜增生过程中缬沙坦对血管紧张素转换酶2（ACE2）表达变化的影响及其机制，探讨ACE2及缬沙坦在再狭窄中的作用。方法将36只Wistar大鼠随机分为对照组、手术组和缬沙坦组，球囊剥脱大鼠主动脉内皮，在术后14和28d分别取其主动脉，并通过组织学检查、放射免疫法、酶联免疫法、逆转录聚合酶链反应和Westernblot技术检测内膜增生的情况、血管紧张素Ⅱ（AngⅡ）、血管紧张素（1—7）[Ang（1—7）]、ACE2、血管紧张素II1型（AT）受体和细胞外信号调节激酶（ERK）的表达水平及缬沙坦（20mg·kg-1·d-1）对它们表达变化的影响。结果（1）手术组大鼠内皮损伤后14d血管平滑肌细胞（VSMC）增殖及内膜增生均明显高于对照组（P均〈0．01），术后28dVSMC增殖减弱，而内膜继续增生。缬沙坦组大鼠治疗14和28dVSMC增殖及内膜增生程度均轻于手术组（P均〈0．05）。（2）手术组大鼠主动脉内皮损伤后14和28dACE2mRNA及蛋白表达明显低于对照组（P均〈0．01），AT．受体mRNA及蛋白表达明显高于对照组（P均〈0．01），AnglI水平明显高于对照组（P〈0．01和0．05），磷酸化ERK水平明显高于对照组，Ang（1—7）水平明显低于对照组（P均〈0．01）。（3）缬沙坦组大鼠主动脉ACE2mRNA及蛋白表达、Ang（1—7）的水平均明显高于手术组（P均〈0．05），AT，受体mRNA及蛋白表达、Ang1I和磷酸化ERK水平明显低于手术组（P均〈0．05）。结论血管内皮损伤后内膜增生的过程中ACE2表达降低，缬沙坦抑制内膜增生的作用与其上调ACE2和Ang（1—7）的表达、下调AT，受体的表达有关。Objective To investigate the process and mechanism of neointimal formation, the level of angiotensin Ⅱ and angiotensin （ 1-7 ） , the expression of angiotensin converting enzyme 2 （ ACE2）, angiotensin Ⅱ type 1 receptor （ATR）, extracellular signal regulated kinase （ERK） and the effects of valsartan on them after aortic balloon injury in rats. Methods Aortic endothelial denudation of rats was induced by 2F balloon catheter. Thirty-six rats were randomly allocated into three groups ： Group 1 （ n = 12） ： controls; Group 2 （n = 12） ： aortic balloon injury; Group 3 （n = 12） ： valsartan （20 mg kg -1 . d -1 ） given from 1 day before injury to 14 and 28 days after aortic injury. The expression of ACE2 and AT1, the level of P-ERK, Ang 11 , Ang （1-7） and intimal thickening were investigated by RT-PCR technique, immunohistochemistry, Western blot, radioimmunological method, enzymelinked immuuosorbent assay ELISA） and HE stain, respectively. Results （1）The proliferation of vascular smooth muscle ceils VSMC ） and the intimal thickening were evidenced at day 14 and 28 after aortic balloon injury. （2）The mRNA and protein expressions of ACE2 decreased significantly, but ATtR mRNA and protein expression increased significantly at day 14 and 28 after balloon injury. （ 3 ） The level of Ang ]I and p-ERK increased and Ang（ 1-7 ） reduced after balloon injury. （4）Valsartan not only attenuated the proliferation of VSMC and the intimal thickening but also upregulated the expression of ACE2 and the level of Ang （ 1-7 ） and downregulated the expression of AT1R and the level of Ang Ⅱ , p-ERK in this model. Conclusion Intimal thickening after balloon injm7 is linked with reduced expression of ACE2. Valsartan can inhibit the intimal thickening possibly by upregulating ACE2 and Ang（ 1-7 ） and downregulating ATl in this model.

关 键 词：血管成形术 气囊 肽基二肽酶A 缬沙坦 

分 类 号：R965[医药卫生—药理学]