苯那普利对糖尿病大鼠肾皮质TGFβ_1及其受体表达的影响

The effect of banazepril on the expressions of TGFβ 1 and its receptor in diabetic rat kidney cortex

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?

AIM To investigate the effect of benazepril on the expressions of TGFβ 1 and its receptor (TβR) in diabetic rat kidney cortex. METHODS The rats were randomly divided into following groups: uninephrectomized (group C), streptozotocin diabetic rats (group D) and diabetic rats treated with benazepril (10 mg·kg -1 ·d -1 , by gavage, group DB). Blood glucose, serum insulin, serum creatinine lever and body weight, kidney weight as well as renal protein protein content were observed after 4 weeks of treatment. ACE activities were measured by spectrofluorimetry in plasma, renal cortex and medulla. mRNA expressions of TGFβ 1, 1α(IV) precollagen and FN were determined by Northern blot; protein expressions of TGFβ 1 and TβRⅠ was measured by Western blot in renal cortex. RESULTS After 4 weeks of treatment, benazepril could significantly ameliorate hyperglycemia, decreased serum insulin, elevated serum creatinine and body weight loss, kidney hypertrophy. Northern blot showed the expressions of TGFβ 1, 1α(IV) precollagen, FN mRNA were increased by 3 94, 4 25 and 1 50 folds, respectively; Western blot showed the expressions of TGFβ 1 amd TβRⅠ were elevated by 3 10 and 1 10 folds. However, benazepril could significantly suppress their expressions. In addition, there was an increase in renal cortex ACE activities despite a decrease in plasma ACE activities. Administration of benazepril could reduce ACE activities in plasma and renal cortex by approximately 92 00%, 88 77%, respectively. CONCLUSION Benazepril could significantly suppress the expressions of TGFβ 1 and its receptor, These might be its main mechanism of nephroprotection in diabetic model.