缬沙坦对糖尿病肾病大鼠足细胞自噬的影响

Effects of valsartan on podocyte autophagy in rats with diabetic nephropathy

目的:研究缬沙坦对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病肾病(diabetic nephropathy,DN)大鼠的改善作用,及对大鼠足细胞自噬的影响。方法:雄性SD大鼠30只,随机分正常组、模型组和缬沙坦组(n=10)。腹腔注射STZ复制糖尿病动物模型,成模后每日灌胃(ig)给予缬沙坦20 mg·kg^(-1),12周后检测24 h尿蛋白定量、空腹血糖、血肌酐和尿素氮。PAS染色观察肾小球病理改变,免疫荧光双染观察Nephrin及LC3共染色情况。Western Blot检测Nephrin,LC3和p62蛋白的表达。结果:与模型组相比,缬沙坦组大鼠24 h尿蛋白减少,Nephrin和LC3-Ⅱ蛋白表达上调,p62蛋白表达下调(P<0.05)。结论:缬沙坦可能通过提高自噬水平保护足细胞,降低蛋白尿,从而延缓DN进展。

Objective：To study the effects of valsartan on kidney and podocytes autophagy in rats with diabetic nephropathy（DN）. Methods： A total of 30 SD rats were randomly divided into 3 groups,that is, normal group, diabetic group, and valsartan group （n = 10）. Diabetic animal were induced by an intraperitoneal injection of STZ. Diabetic rats were given valsartan 20 mg- kg-1 by oral garage once daily for 12 weeks. At the end of experiment, serum glucose, creatinine and urea nitrogen were measured. 24-hour urinary specimens were collected for determining albumin. The kidneys were taken out and renal pathological changes were observed after PAS staining. LC3 and P62 protein, as autophagy markers, as well as nephrin were detected by Western blotting. Immunofluorescence double dye of nephrin and LC3 was used to detect the autophagy of podocytes. Results： Compared with the diabetic model group,valsartan ameliorated glomerular pathological changes, raised the protein expression of nephrin and LC3- II , and decreased the expression of P62 （ P 〈 0.05 ）. Conclusion ： Valsartan has protective effect on the kidney of DN rats, which may be related to its effect of promoting podocyte autophagy.