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  

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

作　　者：易继飞[1] 王全胜[1] 张丽晓[1] 刘建国[1] 李仁康[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院中西医结合科,武汉430022

出　　处：《华中科技大学学报（医学版）》2010年第1期69-72,86,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.30600810)

摘　　要：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,SGK1)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SGK1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SGK1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SGK1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SGK1mRNA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/SGK1/FN通路,这可能是其防治DN小鼠肾纤维化作用的部分机制。Objective To investigate the expression of serum and glucocorticoid inducible kinase 1 （SGKI）and fibronectin （FN） in the renal cortex of diabetic nephropathy mice and the mechanism of dracorhodin percblorate（DP）inhibiting renal fibrosis of diabetic nephropathy. Methods Eight-weeks old C57BL/6 male mice were divided into 6 groups： normal control group,dia betic 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 nephropatby 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 SGK1 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 SGK1 and FN were increased significantly in diabetic nephropathy control group. As compared with diabetic nephropathy control group, the expression levels of SGK1 and FN were reduced significantly in insulin group and DP [20 mg/（kg·d）] group,and the expression of SGK1 was reduced significantly in DP [10 mg/（kg·d）] group. Conclusion DP can inhibit high glucose/SGK1/FN pathway,which may be,in part, the mechanism by which DP prevents and treats renal fibrosis of diabetic nephropathy mice.

关 键 词：血清和糖皮质激素诱导的蛋白激酶1 纤连蛋白 血竭素高氯酸盐 糖尿病肾病 肾纤维化 

分 类 号：R692.3[医药卫生—泌尿科学]