血清和糖皮质激素诱导的蛋白激酶1在糖尿病小鼠肾皮质中的表达变化

Dynamic Expression of Serum-and Glucocorticoid-inducible Kinase 1 in Renal Cortex of Diabetic Mice

目的探索在糖尿病(diabetes mellitus,DM)肾脏病变进程中,血清和糖皮质激素诱导的蛋白激酶1(serumand glucocorticoid-inducible kinase 1,SGK1)在肾皮质中的表达变化。方法采用链脲佐菌素(streptozotocin,STZ)单次腹腔注射诱导小鼠DM模型,设DM组和正常对照(normal control,NC)组,在DM模型1、3、4、6和12周时,检测肾重指数、血糖和糖化血红蛋白(HbA1c),RT-PCR方法检测肾皮质SGK1 mRNA的表达,Western blot法检测肾皮质SGK1蛋白的表达,同时应用免疫组织化学技术检测肾皮质中肾小球的SGK1蛋白的表达。结果与NC组相比,从第1周末起到第12周末DM组小鼠肾重指数、血糖和HbA1c均显著增加;第1周末肾皮质SGK1 mRNA和蛋白以及肾小球中SGK1蛋白的表达即开始上调,到第4周末肾皮质SGK1 mRNA和蛋白表达达到顶峰,第6周至第12周仍有较高表达。结论随DM肾脏病变发展,肾皮质及肾小球中SGK1持续高表达,进一步提示它在DM肾脏病变进程中起重要作用。

Objective To investigate the dynamic expression of serum and glucocorticoid-inducible kinase 1 （SGK1） in renal cortex of diabetic mice. Methods Mice diabetes mellitus （DM） models were established by single intraperitoneal injection of streptozotocin （STZ）. Male C57BL/6 mice of 8 weeks were randomly divided into normal control （NC） group and DM group. Diabetic mice were sacrificed at 1, 3, 4, 6 and 12 weeks after the STZ injection. The ratio of kidney weight, blood glucose and HbAlc were determined. RT-PCR and Western blot were applied to detect the expression of the cortical SGK1 mRNA and protein respectively. Simultaneously the glomerular SGK1 protein was detected by immunohistochemistry. Results The blood glucose, HbA1c and the ratio of kidney weight were all increased in DM group. The expression of cortical and glomerular SGK1 was up-regulated in DM group in comparison with NC group from 1 to 12 weeks, and the level of SGK1 mRNA and protein reached the peak after 4 weeks. Conclusion The expression of renal cortical SGK1 in DM group was kept at a high level during the process of DM, suggesting SGK1 may play an important role in the development of DM-induced nephropathy.