Wang Xuebin, Luo Changqing, Liu Jianshe, Zhang Chun, Wang Yumei, Zhu Zhonghua
Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
J Huazhong Univ Sci Technolog Med Sci. 2005;25(6):651-4. doi: 10.1007/BF02896161.
The expression of serum and glucocorticoid-induced protein kinase in the renal cortex of diabetic rats was examined, and the function of signal transduction mediated by SGK1 in diabetic nephropathy and its modulatiqn by fluvastatin were also investigated. 24 male Wistar rats were randomly divided into normal control group (n = 8), diabetic nephropathy group (n = 8) and fluvastatin-treated diabetic nephropathy group (15 mg/kg/d, n = 8). The metabolic parameters were measured at the 8th week. The expression of transforming growth factor beta1 (TGF-beta1) and fibronectin (FN) was immunohistochemically examined. The expression of SGK1 was detected by RT-PCR and Western blot, and CTGF mRNA was assessed by RT-PCR. As compared to DN, blood glucose, 24-h urinary protein, Cer and kidney weight index were all decreased and the weight was increased obviously in group F. At the same time, mesangial cells and extracellular matrix proliferation were relieved significantly. The levels of cortex SGK1 mRNA and protein were up-regulated, and both TGF-beta1 and FN were down-regulated by fluvastatin. The mRNA of SGK1 was positively correlated with the CTGF, TGF-beta1 and FN. SGK1 expression is markedly up-regulated in the renal cortex of DN group and plays an important role in the development and progress of diabetic nephropathy by means of signal transduction. Fluvastatin suppressed the increased SGK1mRNA expression in renal cortex and postponed the development of diabetic nephropathy.
检测糖尿病大鼠肾皮质中血清和糖皮质激素诱导蛋白激酶的表达，并研究SGK1介导的信号转导在糖尿病肾病中的作用及其受氟伐他汀的调节作用。将24只雄性Wistar大鼠随机分为正常对照组（n = 8）、糖尿病肾病组（n = 8）和氟伐他汀治疗糖尿病肾病组（15 mg/kg/d，n = 8）。在第8周时测量代谢参数。采用免疫组织化学法检测转化生长因子β1（TGF-β1）和纤连蛋白（FN）的表达。通过RT-PCR和Western blot检测SGK1的表达，通过RT-PCR评估CTGF mRNA。与糖尿病肾病组相比，F组血糖、24小时尿蛋白、Cer和肾脏重量指数均降低，体重明显增加。同时，系膜细胞和细胞外基质增生明显减轻。氟伐他汀上调皮质SGK1 mRNA和蛋白水平，下调TGF-β1和FN水平。SGK1的mRNA与CTGF、TGF-β1和FN呈正相关。糖尿病肾病组肾皮质中SGK1表达明显上调，并通过信号转导在糖尿病肾病的发生发展中起重要作用。氟伐他汀抑制肾皮质中SGK1 mRNA表达的增加，延缓糖尿病肾病的发展。
