Effect of Astragaloside Ⅳ on Regulation of PI3K/Akt/FoxO1 Signal in Kidney of Type 2 Diabetic Nephropathy Rats / 中国实验方剂学杂志

ABSTRACT

Objective:To study the protective effect of astragaloside (AS) Ⅳ on kidney in type 2 diabetic nephropathy rats and its regulation effect on phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O1(FoxO1) signaling, and investigate the mechanism of glycosides against type 2 diabetic nephropathy. Method:After 6 weeks of high-glucose and high-fat diet, rat models of type 2 diabetes were established by intraperitoneal injection of streptozotocin (STZ) (35 mg·kg-1) and randomly divided into model group, AS-Ⅳ (20, 40, 80 mg·kg-1) groups and metformin hydrochloride (positive) group. After 8 weeks of continuous administration, changes in body weight, kidney index, blood glucose, 24-hour urinary protein, urinary microalbumin, urinary creatinine, serum creatinine, and blood urea nitrogen were measured in each group; hematoxylin-eosin (HE) staining was used to observe the pathological changes of renal tissues; Masson trichrome staining was used to observe the collagen expression level. Periodontium hexaammine silver (PASM) staining was used to observe the changes of basement membrane. Immunohistochemistry assay was used to detect phospho-FoxO1(p-FoxO1) protein expression, and Western blot was used to analyze the expression levels of autophagy marker protein PI3K, microtubule-associated protein 1 light chain 3 (LC3)/Ⅱ, B-cell lymphoma-2 (Bcl-2)/adenovirus E1B19 kDa interacting protein 3 (BNIP3), Beclin1, p-Akt, and Akt. Result:As compared with the normal group, the glomerular basement membrane of the model group was thicker; the extracellular matrix was increased; the mesangial was expanded; the collagen was significantly increased; the PI3K/Akt/FoxO1 signal was increased(PPPPPPConclusion:AS-Ⅳ may increase the autophagic activity of renal cells by inhibiting PI3K/Akt/FoxO1 signal, slowing down the development of type 2 diabetic nephropathy.