基于PI3K/Akt通路探讨益气化瘀方延缓糖尿病肾脏病的作用机制OA

Objective To explore the role and mechanism of Yiqi Huayu Decoction(益气化瘀方)in delaying diabetic kidney disease via the PI3K/Akt pathway.Methods Thirty-six male SD rats,SPF-grade,were randomly divided into six groups:blank group,model group,dapagliflozin group,and Yiqi Huayu Decoction low,medium and high dose groups,with 6 rats in each group.The model group was constructed by feeding with high sugar and fat and inducing intraperitoneal injection of streptozotocin(STZ).Starting from the beginning of administration,fasting blood glucose(FBG)was measured in rats every two weeks via tail vein sampling.After 8 weeks of administration,blood,urine,and tissue samples were collected from rats to detect 24 h urine protein quantification(24 h UTP),serum creatinine(Scr),serum urea nitrogen(BUN),total cholesterol(TC),triglycerides(TG);Hematoxylin-eosin(HE)and Masson staining to observe the histopathological changes and collagen deposition in rat kidney;Enzyme-linked immunosorbent assay(ELISA)was performed to detect the levels of the interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α);Expression of protein of p-PI3K and p-Akt in rat kidney tissues were measured by immunohistochemistry(IHC).Results After drug intervention,the expressions of FBG,24 h UTP,Scr,BUN,TC,TG in the high-dose Yiqi Huayu Decoction group were significantly lower than those in model group(P<0.01).The results from HE and Masson staining showed that,compared with the blank group,rats in the model group exhibited pathological alterations including enlarged glomerular volume,swollen tubular cells,vacuolar degeneration,and marked collagen deposition.Compared with the model group,Yiqi Huayu Decoction significantly ameliorated pathological damage and reduced collagen deposition in renal tissues of DKD rats.ELISA results demonstrated that,compared with the model group,the expressions of IL-6 and TNF-α in the medium and high dose Yiqi Huayu Decoction groups were decreased(P<0.01).Immunohistochemistry results showed that compared with the blank group,the expression levels of p-PI3K and p-Akt in the model group were increased(P<0.01).Compared with the model group,the expression levels of p-PI3K and p-Akt in the medium and high dose Yiqi Huayu Decoction groups were significantly decreased(P<0.01).Conclusion Yiqi Huayu Decoction can regulate glucose and lipid metabolism disorders,improve renal function,reduce proteinuria,alleviate inflammatory responses,and delay renal tissue injury in DKD rats.Its mechanism may be related to the inhibition of PI3K/Akt pathway activation.