替米沙坦对高血压大鼠血管重构和AngⅡ1型受体表达的影响  

Effects of telmisartan on vascular remodeling and angiotensin Ⅱ typeⅠreceptor expression in experimental hypertensive rat

作　　者：周希[1] 李法琦[2] 余江恒[3] 苟晓燕[4] 

机构地区：[1]重庆市急救医疗中心心内科,重庆400014 [2]重庆医科大学附属第一医院老年科 [3]自贡市第一人民医院心内科 [4]重庆市第一人民医院心内科

出　　处：《中国老年学杂志》2013年第6期1317-1320,共4页Chinese Journal of Gerontology

基　　金：重庆市卫生局医学科研项目(No.03-2-121)

摘　　要：目的探讨替米沙坦对实验性高血压大鼠血管重构和AngⅡ1型受体(AT1R)的影响。方法腹主动脉部分缩窄构建高血压大鼠模型,24只雌雄各半SD大鼠随机分成高血压组和替米沙坦组(3 mg.kg-1.d-1),另设假手术组为对照组。测定血流动力学指标和心室质量指数,主动脉进行图像分析,检测大鼠血浆与主动脉组织匀浆中血管紧张素Ⅱ(AngⅡ)含量,测定主动脉血管内皮细胞、血管平滑肌细胞AT1R蛋白的表达。结果①与假手术组比较,高血压组收缩压(SBP)、舒张压(DBP)、平均动脉压(MABP)、左室质量指数(LVMI)、中膜厚度/内径、中膜面积/内腔面积显著升高(P均<0.05);高血压组大鼠血浆与主动脉组织匀浆中AngⅡ含量和AT1R表达较对照组明显增高(P均<0.05);②高血压组血浆AngⅡ、血管平滑肌细胞AT1R、主动脉中膜厚度/内径比值或中膜面积/内腔面积比值三者之间互为显著正相关(r=0.88～0.93,P<0.01～0.001);主动脉匀浆AngⅡ、血管平滑肌细胞AT1R、主动脉中膜厚度/内径比值或中膜面积/内腔面积比值三者之间亦互为显著正相关(r=0.82～0.91,P<0.01～0.001)。③替米沙坦能显著改善血流动力学指标,降低LVMI、中膜面积/内腔面积(P均<0.05);替米沙坦组主动脉匀浆中AngⅡ水平、血管内皮细胞和平滑肌细胞AT1R均较高血压组降低(P均<0.05)。结论过度表达的AT1R在高血压大鼠血管重构中起到了重要作用,替米沙坦通过抑制AT1R的表达从而逆转血管重构。Objective To investigate the effects of telmisartan on vascular remodeling and angiotensinⅡ（AngⅡ）typeⅠ（AT1）receptor expression in experimental hypertensive rats.Methods Animal model of experimental hypertensive rats were achieved by partially banding abdominal aortic artery.24 SD rats were divided into hypertension and telmisartan（3 mg·kg^-1·d^-1）groups randomly and sham group was as control group.In sixth week,hemodynamic variables and left ventricular mass index（LVMI）were monitored.Aortic image were analyzed.AngⅡ level in plasma and aorta and the expression of AngⅡ and AT1R protein in vascular endothelial cells（VECs）and vascular smooth muscle cells（VSMCs）were measured.Results ①Compared with sham-operated group,systolic blood pressure（SBP）,diastolic blood pressure（DBP）and mean blood pressure（MBP）and LVMI and in the film thickness/diameter and membrane area/cavity area were significantly increased in hypertension group.There was also an obviously increased in AngⅡ level in aorta and plasma and AT1R expression in VEC and VSCM in this group（P0.05）.②There were significant positive correlations among plasma AngⅡ and AT1R and the film thickness/diameter and membrane area/ cavity（r=0.88-0.93,P0.01-0.001）.And aorta AngⅡ level was closely related to the film thickness/diameter and membrane area/cavity and expression of AT1R protein in VSMC of hypertension group（r=0.82-0.91,P0.01-0.001）.③Compared with the operated group,SBP,MBP,LVMI and the membrane area/cavity area and the level of AngⅡin aorta and the AT1R protein expressing of VSMC were significantly reduced in telmisartan group（P0.05）.And aorta AngⅡlevel and AT1R protein expressions of VSMC were significantly reduced in this group（P〈0.05）.Conclusions Overexpression AT1R could contribute to vascular remodeling in experimental hypertensive rats.Telmisartan could reverse vascular remodeling by preventing the protein expression of AT1R in vessel.

关 键 词：替米沙坦 高血压 血管重构 血管紧张素Ⅱ 血管紧张素Ⅱ1型受体 

分 类 号：R544.1[医药卫生—心血管疾病]