选择性内皮素受体拮抗剂对大鼠心肌纤维化保护作用  

Protective effect of selective endothelin receptor antagonist on isoproterenol-induced rats with myocardial fibrosis

作　　者：尚小珂[1] 邓晓娴[1] 周红梅[1] 张刚成[1] 张长东[1] 柳梅[2] 夏成[1] 

机构地区：[1]武汉亚洲心脏病医院心外科,武汉430022 [2]武汉市第一医院ICU,武汉430022

出　　处：《中华实用诊断与治疗杂志》2013年第12期1189-1191,共3页Journal of Chinese Practical Diagnosis and Therapy

基　　金：湖北省卫生厅科研项目(JX6B90);武汉市卫生局科研项目(WX13C47)

摘　　要：目的探讨选择性内皮素受体拮抗剂对大鼠心肌纤维化的保护作用。方法 24只雄性Wistar大鼠随机分为3组各8只,模型组及安立生坦组大鼠背部皮下注射异丙肾上腺素5mg/(kg·d),对照组背部皮下注射等体积生理盐水,连续8d。第9天开始,安立生坦组给予安立生坦40μg/d灌胃,对照组及模型组给予等体积生理盐水灌胃,均1次/d,连续4周,4周后处死大鼠。比较3组大鼠心肌组织及血液中羟脯氨酸(hydroxyproline,Hyp)水平及心肌细胞结构、排列、胶原蛋白增生情况;比较各组大鼠模型左心室收缩压和左心室内压最大上升下降变化速率、血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)、转移生长因子-β1(transfer growth factor-beta 1,TGF-β1)及内皮素-1(endothelin-1,ET-1)的表达水平。结果安立生坦组心肌细胞肿胀、断裂及胶原纤维增生程度明显低于模型组(P<0.05),与对照组比较差异无统计学意义(P>0.05);模型组心肌组织和血液中Hyp水平及AngⅡ、TGF-β1、ET-1表达较安立生坦组和对照组明显增高(P<0.01);模型组左心室收缩压和左心室内压最大上升下降变化速率较安立生坦组和对照组明显降低(P<0.05)。结论选择性内皮素受体拮抗剂可有效阻抑心肌纤维化及心肌重塑的发生、发展,是抗心肌纤维化治疗的合理靶点之一。Objective To discuss the protective effect of selective endothelin receptor antagonist on rats with myocardial fibrosis. Methods Twenty-four healthy adult male Wistar rats were randomly divided into three groups, with 8 rats in each group. Model group and Ambrisentan group were subcutaneously injected isoproterenol 5 mg/（kg·d）, and control group was subcutaneously injected same volume of normal saline, for totally 8 days. From the ninth day, Ambrisentan group received stomach irrigation of ambrisentan 40 μg/d, and model group and control group received normal saline stomach irrigation in the same volume, once a day for totally 4 weeks. All rats were sacrificed after 4 weeks. The content of hydroxyproline （Hyp） in the myocardial tissue and the blood, the myocardial cell structure and arrangement, collagen proliferation, left ventricular systolic pressure, maximal rate of left ventricular pressure development/decline, angiotensin Ⅱ （Ang Ⅱ ）, transfer growth factor beta 1 （TGF-β1） and endothelin-1 （ET-1） were compared among three groups. Results The degrees of myocardial cell swelling, rupture and collagen proliferation in Ambrisentan group were similar to control group （PT〉0.05）, significantly lower than those in model group （P〈0.05）. The Hyp contents, and the levels of Ang lI , TGF-131 and ET-1 in myocardial tissue and blood were higher in model group than those in control group and Ambrisentan group （P〈0. 01）. Left ventricular systolic pressure and maximal rate of left ventricular pressure development/decline were significantly lower and in model group than those in Ambrisentan group and control group （P〈 0.05）. Conclusion Selective endothelin receptor antagonist can effectively inhibit myocardial fibrosis, as well as the development and progression of myocardial remodeling, and it is one of the reasonable targets to resist myocardial fibrosis.

关 键 词：心肌纤维化 大鼠 选择性内皮素受体拮抗剂 内皮素-1 血管紧张素-Ⅱ 

分 类 号：R542.23[医药卫生—心血管疾病]