[Yiqi Yangyin Tongluo Recipe(YYTR)alleviates renal injury in diabetic nephropathy rats by inhibiting PI3K/AKT pathway and aquaporin 2 (AQP2)].

ABSTRACT

Objective To explore the effects of Yiqi Yangyin Tongluo Recipe (YYTR) on the expressions of phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) and aquaporin 2(AQP2) in diabetic renal tissue and its mechanism. Methods Sixty Wistar rats were randomly divided into the blank group, model group, valsartan (20 mg/kg) group, YYTR (4 mg/kg or 1 mg/kg), 4 mg/kg YYTR combined with 0.5 µmol/kg 740Y-P group, with 10 rats in each group. Except the blank group, the rats in other groups were fed with high-glucose and high-fat diet and injected with streptozocin to create diabetic nephropathy (DN) rat models. The day after successful modeling, the rats were administrated intragastrically for 8 weeks. At the end of the experiment, renal function indexes were measured, and glomerular sclerosis index and renal interstitial injury index were evaluated according to the results of HE staining and Masson staining. Western blot analysis was used to detect the levels of AQP2, PI3K, AKT, p-PI3K and p-AKT. Immunohistochemical staining was used to detect the expression and distribution of AQP2 in renal tissue. Results Compared with the normal group, urine protein quantitation in 24 hours (24 h UTP), serum creatinine, urea nitrogen and ß2-microglobulin (ß2-MG) content in model group were increased. It also reported a rise of kidney index, glomerulo sclerosis index, renal interstitial injury index, AQP2 protein and PI3K, AKT, p-PI3K and p-AKT protein expressions in model group. But compared with model group, the above indexes all decreased in 4 mg/kg YYTR group. In addition, compared with 4 mg/kg YYTR group, the above indexes in YYTR combined with 740Y-P group were increased. Conclusion YYTR can protect renal function by down-regulating AQP2 protein expression and inhibiting PI3K/AKT signaling pathway activation.