血竭素高氯酸盐抑制高糖/SGK_1/FN通路防治糖尿病肾病小鼠肾纤维化

目的 研究血清和糖皮质激素诱导的蛋白激酶1(serum and glucocorticoid inducible kinase 1,SGK_1)及其下游分子纤连蛋白(fibronectin,FN)在糖尿病肾病(diabetic nephropathy,DN)小鼠肾皮质中的表达以及血竭素高氯酸盐(dracohodin perchlorate,DP)抑制DN肾纤维化的机制.方法 采用链脲佐菌素(streptozotocin,STZ)建立C57BL/6小鼠糖尿病肾病模型,设正常对照组、糖尿病肾病对照组、胰岛素治疗组及血竭素高氯酸盐5、10、20 mg/(kg·d)3种剂量治疗组,分别干预4周后,用RT-PCR、Western blot或免疫组化方法 检测各组小鼠肾皮质中SGK_1和FN mRNA及蛋白的表达水平.结果与正常组比较,糖尿病肾病模型组中SGK_1和FN mRNA及蛋白的表达水平显著性增高;与糖尿病肾病模型组比较,胰岛素治疗组和血竭素高氯酸盐20 mg/(kg·d)治疗组中SGK_1和FN mRNA及蛋白的表达水平显著降低,血竭素高氯酸盐10 mg/(kg·d)治疗组中SGK_1mRNA及蛋白的表达水平显著降低.结论 血竭素高氯酸盐能抑制高糖/SGK_1/FN通路,这可能是其防治DN小鼠肾纤维化作用的部分机制.

Prevention and Treatment of Renal Fibrosis of Diabetic Nephropathy Mice with Dracorhodin Perchlorate by Inhibiting High Glucose/SGK1/Fibronectin Pathway

Objective To investigate the expression of serum and glucocorticoid inducible kinase 1(SGK_1)and fibronectin(FN)in the renal cortex of diabetic nephropathy mice and the mechanism of dracorhodin perchlorate(DP)inhibiting renal fibrosis of diabetic nephropathy.Methods Eight-weeks old C57BL/6 male mice were divided into 6 groups:normal control group,diabetic nephropathy control group,disease mice administered with insulin group,disease mice group with DP at the concentrations of 5,10,and 20 mg/(kg·d).Diabetic nephropathy in mice was induced by streptozotocin(STZ)150 mg/kg peritoneal injection,and the mice were killed after treatment for four weeks.The expression levels of SGK_1 and FN mRNA and protein were detected by semi-quantitative RT-PCR and Western blot or immunohistochemistry,respectively.Results As compared with normal control group,the expression levels of SGK_1 and FN were increased significantly in diabetic nephropathy control group.As compared with diabetic nephropathy control group,the expression levels of SGK_1 and FN were reduced significantly in insulin group and DP [20 mg/(kg · d)] group,and the expression of SGK_1 was reduced significantly in DP [10 mg/(kg · d)] group.Conclusion DP can inhibit high glucose/SGK_1/FN pathway,which may be,in part,the mechanism by which DP prevents and treats renal fibrosis of diabetic nephropathy mice.