厄贝沙坦对高血压左室肥厚家兔跨心室壁Cx43蛋白异质性的影响  

Effects of irbesartan on transmural heterogeneous of Cx43 in rabbit with left ventricular hypertrophy

作　　者：钟江华[1] 陈小盼[1] 何喜民[1] 黄珊[1] 林云[1] 陆士娟[2,3] 

机构地区：[1]海南医学院附属医院心血管内科,海南海口570102 [2]中南大学湘雅医学院附属海口医院心血管内科,海南海口570208 [3]海口市人民医院心血管内科,海南海口570208

出　　处：《沈阳药科大学学报》2013年第9期713-717,共5页Journal of Shenyang Pharmaceutical University

基　　金：2012年海口市重点科技项目(2012-077)

摘　　要：目的观察血管紧张素受体拮抗剂(angiotensin receptor blocker,ARB)厄贝沙坦对高血压左室肥厚(left ventricular hypertrophy,LVH)家兔左心室心肌跨室壁复极不均一性及Cx43蛋白分布异质性的影响,探讨ARB在LVH恶性室性心律失常(malignant ventricular arrhythmias,MVA)治疗中的作用。方法将20只家兔随机分成LVH实验组和厄贝沙坦治疗组,每组10只。两组均采用传统的腹主动脉缩窄术制备家兔LVH模型。对照组继续喂养8周,厄贝沙坦治疗组手术后除普通喂养外还给予经口喂服厄贝沙坦片,每次10mg·kg-1,每天1次,连续8周,然后进行实验。分别检测两组家兔的室颤阈值(ventricular fibrillation threshold,VFT)及心外膜下、中层心肌和心内膜下心肌细胞的单相动作电位复极90%时程(APD90)、跨室壁复极离散度(transmural dispersion of repolarization,TDR)以及三层心肌Cx43蛋白表达的差异。结果厄贝沙坦治疗组的平均动脉压、心质量/体质量指数和左心室壁厚度与LVH实验组对比明显下降(P<0.05)。厄贝沙坦治疗组的VFT明显高于LVH实验组(P<0.05),TDR和△APD90则显著缩小(P<0.05)。与LVH实验组比较,厄贝沙坦治疗组中层心肌、心外膜下心肌和心内膜下心肌的Cx43蛋白表达均有明显增加(P<0.05),但以中层心肌的增加更为明显,△Cx43缩小。结论厄贝沙坦能改善高血压左室肥厚的跨室壁Cx43表达异质性,使左心室心肌跨室壁复极不均一性增大,VFT下降,减少MVA的发作。Objective To observe the effects of irbesartan on transmural heterogeneity of Cx43 expression in the rabbit model with left ventricular hypertrophy, and investigate the treatment and mechanisms of malignant ventricular arrhythmias （MVA） induced by left ventricular hypertrophy （LVH）. Methods Twenty rabbits were randomly divided into LVH group （n = 10） and irbesartan group （n = 10）. LVH model was produced with traditional abdominal aortic coarctation in the both group. Rabbits in the LVH group were continue to feed for 8 weeks after surgery,and given feeding irbesartan tablets （10 mg.kg-l.d-1） for eight consecutive weeks after surgery in the irbesartan group. Ventricular fibrillation threshold （VFT）, 90% monophasic ac- tion potential repolarization duration （APDg0） of subepicardial, midmyocardial and subendocardial myocar- dium, transmural dispersion of repolarization （TDR） and Cx43 protein expression in three layers of myocar- dium were measured in both groups. Results Mean arterial pressure, heart weight/body mass index and thickness of left ventricular wall in the irbesartan group were significant improved compared with the LVH group （P 〈 0. 05 ）. VPT in the irbesartan group was significantly higher than that in the LVH group （ P 〈 0. 05 ）, and TDR and AAPDg0 in the irbesartan group significantly reduced compared with the LVH group （ P 〈 0. 05 ）. Compare with the LVH group, three myocardial Cx43 protein expression in the irbesartan group were significantly increased （P 〈 0.05 ）, especially increasing in the midmyocardium was more significant and A Cx43 decline. Conclusions Irbesartan can increase transmural heterogeneity of Cx43 expression and decrease VP-T, which make it more easily induced MVA.

关 键 词：中层心肌 缝隙连接蛋白43 左室肥厚 血管紧张素Ⅱ 

分 类 号：R96[医药卫生—药理学]