咪达普利与氯沙坦对糖尿病大鼠心肌间质重构的对比研究  

Comparison of Imidapril and Losartan in Improving Myocardial Interstitial Remodeling of Diabetic Rats

作　　者：张晗[1] 熊世熙[1] 雷红[1] 曹建雷[1] 曹新营[1] 宋志明[1] 

机构地区：[1]武汉大学中南医院心内科,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2010年第1期71-75,共5页Medical Journal of Wuhan University

基　　金：湖北省卫生厅重点研究项目(编号:JX2A19);国家大学生创新性实验项目(编号:武汉大学2007065)

摘　　要：目的:研究在不同水平阻断肾素-血管紧张素系统(RAS)对糖尿病大鼠心肌间质重塑过程的影响及保护机制。方法:50只健康雄性SD大鼠随机分为空白对照组(10只)和糖尿病组(40只),糖尿病组用链脲佐菌素(STZ)50 mg/kg腹腔注射建立实验性糖尿病大鼠模型,将建模成功的39只大鼠随机分为咪达普利组10只、氯沙坦组10只、联合用药组10只及模型对照组9只,给药9周后麻醉处死,免疫组化SP法检测肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)、基质金属蛋白酶-9(MMP-9)的蛋白表达,RT-PCR法测NF-κB、MMP-9和TNF-α的mR-NA表达。VG染色观察心肌胶原容积分数(CVF)变化。结果:与空白对照组相比,糖尿病组大鼠心脏指数、左心室指数、心肌CVF明显升高,心肌间质发生重构,TNF-α、MMP-9、NF-κB含量和TNF-αmRNA、MMP-9 mRNA和NF-κB mRNA的表达均增高。咪达普利、氯沙坦及联合用药干预后,上述指标表达均明显降低,但咪达普利和氯沙坦的改善程度无明显差异,联合用药明显优于单独用药。结论:咪达普利和氯沙坦可能通过影响TNF-α、MMP-9的表达来改善糖尿病心肌间质重构,NF-κB参与了这一过程。Objective： To investigate the change of myocardial interstitial remodeling in diabetic rats by inhibiting the renin-angiotensin system in different levels. Methods： A total of 39 SD diabetic rats, which were established by intraperitoneal injection of streptozotocin （STZ）, were divided into diabetic model group （n=9）,imidapril treated group （n=10）, losartan treated group （n= 10）, and imidapril＋losartan treated group （n=10）. Immunohistochemistric method was used to measure the expression of tumor necrosis factor-alpha （TNF-α）,nuclear faetor-κB （NF-κB） and matrix metalloproteinases-9 （MMP-9）. The levels of MMP-9 mRNA,TNF-α mRNA and NF-κB mRNA were measured by RT-PCR. Cardiac collagen contents were analyzed by Van Gieson （VG） staining and the results were quantified by densitometry. Results： At the end of expriment, the cardiac index and the ventricle index were significantly higher in the model group than in the normal （P（0.05）. VG staining showed a marked deposition of collagen in diabetic group. The expression of TNF-α, MMP-9, NF-κB protein and mRNA were also significantly higher than in normal rats. All those indexes were greatly improved in the treatment groups, especially in imid- aprilq-losartan treated group, than in diabetic model group. Conclusion： Losartan and imidapril could inhibit the renin-angiotensin system in protein and mRNA level, influence the expression of TNF-α and MMP-9 ; NF-κB may take part in this procedure, and reverse the myocardial intersti- tial remodeling of diabetic rats.

关 键 词：心肌间质重构 肿瘤坏死因子 核因子-ΚB 基质金属蛋白酶 咪达普利 氯沙坦 

分 类 号：R587.1[医药卫生—内分泌]