CAJ | 학술논문

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28 d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Western blot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( AT1)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14 d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28 d VSMC增殖减弱,而内膜继续增生.缬沙坦组大鼠治疗14和28 dVSMC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28 d ACE2 mRNA及蛋白表达明显低于对照组(P均＜0.01),AT1受体mRNA及蛋白表达明显高于对照组(P均＜0.01).AngⅡ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ACE2 mRNA及蛋白表达、Ang( 1-7)的水平均明显高于手术组(P均＜0.05),AT1受体mRNA及蛋白表达、AngⅡ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AT1受体的表达有关.
목적 연구혈관내피구낭손상후혈관내막증생과정중힐사탄대혈관긴장소전환매2( ACE2)표체변화적영향급기궤제,탐토ACE2급힐사탄재재협착중적작용.방법 장36지Wistar대서수궤분위대조조、수술조화힐사탄조,구낭박탈대서주동맥내피,재술후14화28 d분별취기주동맥,병통과조직학검사、방사면역법、매련면역법、역전록취합매련반응화Western blot기술검측내막증생적정황、혈관긴장소Ⅱ( AngⅡ)、혈관긴장소(1-7)[Ang(1-7)]、ACE2、혈관긴장소Ⅱ1형( AT1)수체화세포외신호조절격매(ERK)적표체수평급힐사탄(20mg· kg-1 ·d-1)대타문표체변화적영향.결과 (1)수술조대서내피손상후14 d혈관평활기세포(VSMC)증식급내막증생균명현고우대조조(P균＜0.01),술후28 d VSMC증식감약,이내막계속증생.힐사탄조대서치료14화28 dVSMC증식급내막증생정도균경우수술조(P균＜0.05).(2)수술조대서주동맥내피손상후14화28 d ACE2 mRNA급단백표체명현저우대조조(P균＜0.01),AT1수체mRNA급단백표체명현고우대조조(P균＜0.01).AngⅡ수평명현고우대조조(P＜0.01화0.05),린산화ERK수평명현고우대조조,Ang(1-7)수평명현저우대조조(P균＜0.01).(3)힐사탄조대서주동맥ACE2 mRNA급단백표체、Ang( 1-7)적수평균명현고우수술조(P균＜0.05),AT1수체mRNA급단백표체、AngⅡ화린산화ERK수평명현저우수술조(P균＜0.05).결론 혈관내피손상후내막증생적과정중ACE2표체강저,힐사탄억제내막증생적작용여기상조ACE2화Ang(1-7)적표체、하조AT1수체적표체유관.
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 (AT1R),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 Ⅱ,Ang ( 1-7 ) and intimal thickening were investigated by RT-PCR technique,immunohistochemistry. Western blot, radioimmunological method, enzymelinked immunosorbent assay (ELISA) and HE stain,respectively.Results (1)The proliferation of vascular smooth muscle cells (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 AT1R mRNA and protein expression increased significantly at day 14 and 28 after balloon injury.(3) The level of Ang Ⅱ 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 AT1 R and the level of Ang Ⅱ,p-ERK in this model.Conclusion Intimal thickening after balloon injury is linked with reduced expression of ACE2.Valsartan can inhibit the intimal thickening possibly by upregulating ACE2 and Ang(1-7) and downregulating AT1 in this model.