基于PI3K/Akt/mTOR通路的白芍总苷调控自噬对糖尿病肾病大鼠足细胞损伤保护作用及机制研究OA

Objective To investigate the protective effect of total glucosides of paeony(TGP)on podocyte injury in rats with diabetic kidney disease(DKD)by regulating autophagy via the PI3K/Akt/mTOR pathway.Methods Sprague-Dawley(SD)rats were divided into a blank control group and a model establishment group.Rats in the model establishment group were fed a high-glucose and high-fat diet(HFD)for 4 weeks,and diabetic models were established with streptozotocin(STZ,30 mg·kg⁻¹).After successful establishment of dia-betes,the rats were continuously fed a high-glucose and high-fat diet for another 6 weeks.Rats with blood glucose≥16.7 mmol/L for three consecutive tests and 24-hour urinary total protein(24h-UTP)>30 mg were identified as DKD rats.DKD rats were randomly divided into a model group,low/medium/high-dose TGP groups,and a metformin group,all receiving intragastric administration.The blank control group and model group were given an equal volume of distilled water once daily for 4 consecutive weeks.A biochemical analyzer was used to determine the levels of fasting blood glucose(FBG),serum creatinine(SCr),blood urea nitrogen(BUN),24h-UTP and uric acid(UA).HE and Masson staining were used to observe pathological changes in renal tissues.Transmission electron microscopy(TEM)was used to observe the ultrastructure of podocytes.ELISA was used to detect serum levels of IL-6 and IL-1β.West-ern blot(WB)was used to detect the expression of related proteins in renal tissues.Results Compared with the blank control group,the model group showed significantly elevated levels of FBG,24h-UTP,SCr,BUN,UA and serum inflammatory factors IL-6 and IL-1β(P<0.01).Obvious pathological changes were found in renal tissues,and podocyte loss and extensive foot process fusion were observed under electron microscopy.The protein expression of Beclin-1 and the ratio of LC3-II/LC3-I were decreased,while the expres-sion of p-Akt and p-mTOR was significantly increased(P<0.01).Compared with the model group,the low-dose TGP group showed significantly reduced 24h-UTP and IL-6 levels(P<0.01).The medium-dose TGP group showed significantly decreased levels of BUN,IL-6,PI3K,p-Akt and p-mTOR(P<0.01,P<0.05).The high-dose TGP group exhibited markedly decreased levels of SCr,BUN,UA,serum IL-6 and IL-1β(P<0.01),significantly increased expression of Beclin-1 and the ratio of LC3-II/LC3-I,and mark-edly decreased expression of PI3K,p-Akt and p-mTOR(P<0.01,P<0.05).Conclusion TGP exerts a certain protective effect on renal podocyte injury in DKD rats.Its mechanism may be related to inhibiting the PI3K/Akt/mTOR pathway and enhancing autophagic activity.