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目的研究培哚普利(Perindopril)对糖尿病(Diabetes mellitus,DM)大鼠心肌病变及转化生长因子β1(TGF-β1)表达的影响。方法36只雄性SD大鼠随机分为正常对照组(NC,n=12)和糖尿病组(DC,n=24),4周后再分为糖尿病对照组(DC,n=12)和培哚普利治疗组[DP,n=12,2mg/(kg·d)]。治疗12周后,检测血糖、AngII浓度;电镜观察心肌超微结构改变;RT-PCR检测TGF-β1mRNA水平。结果DC组的血糖、血浆和心肌AngII、心肌TGF-β1mRNA、左室重量指数(LVMI)均明显高于NC组,而DP组则均低于DC组,差异有显著性(P<0.01);DM大鼠出现了心肌肥厚和超微结构改变,其病变程度与心肌AngII水平呈一致性,而DP组心肌病变明显减轻。结论培哚普利可能通过降低AngII水平,下调心肌TGF-β1表达而逆转糖尿病大鼠的心肌肥厚和超微结构改变,对糖尿病大鼠心肌病变有治疗作用。
Objective To study the effect of perindopril on the pathological changes of myocardium and the expression of transforming growth factor β1 (TGF-β1) in diabetic mellitus (DM) rats. Methods Thirty - six male Sprague - Dawley rats were randomly divided into normal control group (n = 12) and diabetic group (n = 24), and then divided into diabetic control group (n = 12) Puli treatment group [DP, n = 12, 2 mg / (kg · d)]. After 12 weeks of treatment, blood glucose and AngII levels were measured. Ultrastructural changes of myocardium were observed by electron microscope. The level of TGF-β1 mRNA was detected by RT-PCR. Results The levels of blood glucose, plasma AngⅡ, myocardial TGF - β1 mRNA and LVMI in DC group were significantly higher than those in NC group (P <0.01), while those in DP group were significantly lower than those in DC group (P <0.01). Cardiac hypertrophy and ultrastructure changes were observed in DM rats. The degree of myocardial infarction was consistent with the level of myocardial AngII in diabetic rats, but the myocardial lesions in DP group were significantly reduced. Conclusions Perindopril can reduce the level of AngII and down-regulate the expression of TGF-β1 in myocardium and reverse the changes of cardiac hypertrophy and ultrastructure in diabetic rats, which may have a therapeutic effect on myocardial lesions in diabetic rats.