温度敏感性水凝胶携带阿利吉仑对心肌梗死后大鼠左室重构的影响  

Effects of aliskren with thermosensitive hydrogel on rat ventricular remodeling after myocardial infarction

作　　者：刘杨[1] 李晓艳[1] 蒋学俊[1] 陈盼盼[1] 李君[1] 贺伟[1] 

机构地区：[1]武汉大学人民医院,武汉430000

出　　处：《实用药物与临床》2015年第1期18-23,共6页Practical Pharmacy and Clinical Remedies

基　　金：国家自然科学基金(81170307)

摘　　要：目的探讨水凝胶携带肾素抑制剂阿利吉仑对心肌梗死后大鼠心室重构的影响。方法 70只Wistar大鼠随机分成5组:假手术组(Sham组,0只)、磷酸缓冲液组(Pbs组,15只)、磷酸缓冲液+阿利吉仑组(Pbs+a组,15只)、水凝胶组(Gel组,15只)和水凝胶+阿利吉仑组(Gel+a组,15只),后4组大鼠分别在心梗模型制作成功后,于心肌梗死区周边注射等体积的磷酸缓冲液、含有1.5 mg阿利吉仑的磷酸缓冲液、1.5%的温度敏感性水凝胶和含有1.5 mg阿利吉仑的1.5%温度敏感性水凝胶;而假手术组只穿线不结扎,心肌梗死4周后,用病理切片方法统计心梗面积和胶原容积分数;Western blot的方法检测心肌梗死后心肌组织中MMP-2、M M P-9、TIM P、TGF-β的蛋白含量。结果心肌梗死4周后,56只大鼠存活,其中Sham组8只、Pbs组11只、Pbs+a组12只、Gel组12只、Gel+a组13只;Gel+a组的心梗面积和胶原容积分数明显低于Pbs组(P<0.01);心肌组织中MMP-2、MMP-9、TGF-β的蛋白含量明显低于Pbs组(P<0.05);而心肌组织中TIMP的含量明显高于Pbs组(P<0.05);Gel+a组这些作用被进一步增强。结论温度敏感性水凝胶携带阿利吉仑比单纯应用水凝胶更能改善心肌梗死后大鼠的心室重构,具有协同的心肌保护作用。其可能机制是通过影响MMP-2、MMP-9、TIM P-1的活性及下调TGF-β的表达来影响胶原代谢,减少胶原的合成来改善心室重构及心肌梗死后的心功能。Objective To investigate the effects of aliskren with thermosensitive hydrogel on rat ventricular remodeling after myocardial infarction. Methods Seventy male Wistar rats were randomly divided into five groups,Sham group（ n = 10）,phosphate buffer solution group（ Pbs group,n = 15）,phosphate buffer solution with aliskren group（ Pbs ＋ a group,n = 15）,thermosensitive hydrogel group（ Gel group,n = 15）,thermosensitive hydrogel with aliskren group（ Gel ＋ a group,n = 15）,the four groups（ Pbs gourp,Pbs ＋ a gourp,Gel group,Gel ＋ a group） were respectively injected 75 μL phosphate buffer solution,75 μL phosphate buffer solution with aliskren,75 μL thermosensitive hydrogel and 75 μL thermosensitive hydrogel with aliskren into the infarct area of rats after myocardial infarction.Four weeks later,the infarction area percentage and collagen volume fraction after separation of the heart were calculated. Protein expression of MMP-2,MMP-9,TIMP-1 and TGF-β were determined by Western blotting. Results There were 56 rats survived after myocardial infarction： Sham group,n = 8; Pbs group,n = 11; Pbs ＋ a group,n = 12; gel group,n = 12; Gel ＋ a group,n = 13. The infarction area percentage and the collagen volume fraction was significantly lower in Gel ＋ a group than Pbs group（ P 0. 01）. Compared with the Pbs group,the protein expression of MMP-2,MMP-9,TGF-β were higher in Gel ＋ a group（ P 0. 05）,and the protein expression of TIMP was lower than Pbs group. Conclusion Aliskren with thermosensitive hydrogel can improve ventricular remodeling and cardiac function by regulating down the expression of MMP-2,MMP-9,TGF-β and regulating up TIMP-1 after myocardial infarction.

关 键 词：阿利吉仑 温度敏感性水凝胶 心肌梗死 心室重构 

分 类 号：R542.22[医药卫生—心血管疾病]