摘要
目的 探讨氯沙坦对糖尿病大鼠肾小球信号转导和转录活化因子 3 (STAT3)及STAT3 mRNA表达的影响。 方法 30只大鼠随机分成正常对照组、糖尿病组和氯沙坦治疗组(每日灌胃给予氯沙坦40 mg/kg,共2周)。腹腔注射STZ诱发糖尿病大鼠模型,采用免疫组化和 West ern印迹检测磷酸化 STAT3(p-STAT3)蛋白表达,Western印迹检测 STAT3 蛋白表达,半定量 RT PCR检测STAT3 mRNA的表达。 结果 糖尿病组肾小球 STAT3、p-STAT3 及 STAT3 mRNA表达较正常对照组明显增强;氯沙坦治疗组 p-STAT3 表达较糖尿病组降低,但对 STAT3 蛋白及STAT3 mRNA的表达无明显影响。 结论 氯沙坦的肾脏保护作用可能是部分通过影响 STAT3磷酸化,抑制信号通道而发挥作用。
Objective To investigate the effects of losartan on activation of signal transducers and activators of transcription of STAT3 and mRNA expression of STAT3 in glomeruli of diabetic rats. Methods STZ-induced Wistar diabetic rats were randomly divided into two groups: untreated diabetes group, treated group by losartan 40 mg/kg in addition to normal control group. The renal cortical tissues were obtained and used to isolate glomeruli. The protein expression of p-STAT3 in glomeruli was observed by immunohistochemistry and Western blot. The protein expression and (mRNA) of STAT3 were observed by Western blot and RT-PCR separately. Results The expressions of STAT3, p-STAT3 and STAT3 mRNA were significantly increased in the diabetic glomeruli without losartan treatment vs diabetic group(P<0.01). The expression of p-STAT3 was decreased in losartan group vs control (P<0.05). However, losartan had no effect on the expression of STAT3 and STAT3 mRNA. Conclusion STAT3 signal pathway may be involved in diabetic nephropathy. (Regulation) of phosphorylation of STAT3 may be responsible for the renal protective effects of losartan in diabetic rats.
基金
河北省自然科学基金(C2004000536)