苯那普利对糖尿病大鼠肾皮质TGFβ1及其受体表达的影响

来源 :中国药理学通报 | 被引量 : 0次 | 上传用户:liwang0113
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目的探讨苯那普利对糖尿病大鼠肾皮质TGFβ1及其受体表达的影响。方法大鼠随机分单侧肾切除组(C组);糖尿病组(D组)及糖尿病苯那普利治疗组(10mg·kg-1·d-1,灌胃,DB组),观察4wk后各组血糖、血胰岛素、血肌酐水平及体重、肾重和肾组织蛋白含量的变化,采用荧光分光光度法测定血浆及肾皮质、髓质ACE活性。应用Northern杂交检测各组肾皮质TGFβ1,1α(IV)前胶原及FNmRNA表达;Western杂交检测各组肾皮质TGFβ1及细胞膜TβRⅠ蛋白表达。结果苯那普利治疗4wk后能够明显缓解糖尿病大鼠高血糖、低胰岛素血症、血肌酐水平上升及体重下降、肾脏肥大。Northern杂交表明糖尿病大鼠肾皮质TGFβ1、1α(IV)前胶原及FNmRNA表达分别3.94、4.25及1.50倍,Western杂交表明肾皮质TGFβ1及细胞膜TβRⅠ蛋白表达分别上调3.10、1.00倍,苯那普利治疗4wk后对它们均有明显抑制作用。另外,尽管糖尿病大鼠血浆ACE活性明显下降,肾皮质ACE活性却明显增加,苯那普利治疗后对血浆及肾皮质ACE活性抑制分别达92.00%和88.70%。结论苯那普利可抑制高血糖状态下肾皮质TG? Objective To investigate the effects of benazepril on the expression of TGFβ1 and its receptor in renal cortex of diabetic rats. Methods The rats were randomly divided into three groups: group C (C group), diabetic group (D group) and benazepril treatment group (10 mg · kg -1 · d -1, intragastrically and DB group) Blood glucose, blood insulin, serum creatinine, body weight, renal weight and renal tissue protein content in each group were measured. The ACE activity in plasma, renal cortex and medulla was measured by fluorescence spectrophotometry. Northern blot was used to detect the expression of procollagen and FN mRNA of TGFβ1 and 1α (IV) in renal cortex of each group. Western blotting was used to detect the expression of TGFβ1 and TβRI in renal cortex. Results After benazepril treatment 4wk can significantly relieve diabetic rats hyperglycemia, hypoproteinemia, serum creatinine levels and weight loss, renal hypertrophy. Northern blot showed that the expression of procollagen and FN mRNA of TGFβ1 and 1α (IV) in diabetic rat renal cortex were 3.94, 4.25 and 1.50 fold, respectively. Western blot showed that the expression of TGFβ1 and TβRI in renal cortex were increased by 3.10, 1.00 times, benazepril treatment 4wk after they were significantly inhibited. In addition, although ACE activity was significantly decreased in diabetic rats, ACE activity was significantly increased in renal cortex, and the inhibitory effect on ACE activity in plasma and renal cortex was 92.00% and 88.70% respectively after benazepril treatment. Conclusion benazapril can inhibit renal cortex TG in hyperglycemic state.
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