雷帕霉素对糖尿病肾病大鼠组织TGF-β1及OPN表达的影响

目的:观察雷帕霉素对糖尿病肾病大鼠组织TGF-β1及OPN表达的影响。方法:Wistar大鼠一次性腹腔注射链脲佐菌素(STZ)诱发DN大鼠模型。大鼠随机分三组,分别为:对照组、模型组和雷帕霉素治疗组,给药8周,实验第2,4,8周,测定24h尿蛋白定量;治疗8周后,定时定量PCR法测肾小管间质OPN mRNA表达;免疫组化法检测肾小管间质TGF-β1表达。结果:与正常组比较,模型组大鼠24h尿蛋白定量明显升高(P<0.05),肾组织TGF-β1、OPN表达明显增加(P<0.01)。雷帕霉素治疗组大鼠24h尿蛋白定量明显降低,肾小管间质组织OPN、TGF-β1表达减少,与模型组比较均有显著性差异(P<0.05)。结论:雷帕霉素能减少DN大鼠尿蛋白,下调肾小管间质组织OPN、TGF-β1表达水平,减轻DN肾小管间质病变。

Effect of rapamycin on the expression of transforming growth factor and osteopontin in the diabetic nephropathy rats

Objective：To observe the effect of rapamycin on the expression of TGF--β1 and OPN in rat tis- sues with diabetic nephropathy. Methods：Wistar rats with unilateral resection of the kidney and one--time intraperitoneal injection of streptozotoein （STZ） in DN rats model. The rats were randomly divided into three groups respectively： control group, model group and rapamycin treatment group, being administered for 8 weeks. In the 2nd, 4th, and 8th weeks of the experiment, quantitative determination of 24h urinary protein were done ; 8 weeks after treatment, timing and quantitative P C R method was used to measure renal tubuloin- terstitial O PN mRNA expression; immunohistochemical method was used for detection of renal tubular inter- stitial TGF--β1 expression. Results： Compared with the normal group, 24h quantity of urinary protein of model group rats was significantly elevated （P 〈0.05）, and TGF--β1, O P N expression was significantly in- creased （P 〈 0.01）. 24 h quantity of urinary protein of rapamycin treated group was significantly reduced, and O P N, TGF beta 1 expression in renal tubules and interstitial tissue is reduced, too. Compared with the model group, it showed significant difference （P 〈0.05）. Conclusion： Rapamycin can reduce not only urinary protein of D N rat, but also the O P N, TGF--β1 expression levels of renal tubular interstitial tissue, and the DN renal tubulointerstitial lesions as well.