AIM:To investigate the effect of drug-containing serum of oxytropis falcata extract on oxi-dative stress injury of podocyte induced by high glucose through PI3K/AKT/Nrf2 pathway.METH-ODS:The rat renal podocyte was cultured in vitro,and the concentration and time of D-glucose mod-elling and the optimal concentration and time of administration in the drug-containing serum of oxy-tropis falcata extract were screened.The cells were divided into normal group,high glucose group,high glucose+blank serum group,oxytropis falcata group,inhibitor group,oxytropis falcata+inhibitor group.Rhodamine staining and electron microsco-py were used to observe the morphological and pathological changes of podocyte,flow cytometry was used to detect apoptosis rate,and cell migra-tion ability was detected by scratch test.Immuno-fluorescence and fluorescence probe were used to detect the fluorescence expression of p-AKT and ROS level of cells,ELISA was used to detect the con-tent of MDA,NO,SOD and T-AOC in the superna-tant of cells,and Western Blot was used to detect the protein expression of p-PI3K/PI3K,p-AKT/AKT and Nrf2 in cells.The mRNA expressions of Nrf2,HO-1,GCLM and SOD were detected by RT-qPCR.RESULTS:It was selected that 45 mmol/LD-glucose induction for 48 hours was the best modeling con-dition,and the 1-fold dilution of the medicated se-rum of oxytropis falcata extract for 48 hours was the best concentration and intervention time.Com-pared with the normal group,the foot processes of the high glucose group were widely fused and ad-hered to each other,the apoptosis rate,migration ability and intracellular ROS level were significantly increased(P＜0.01),the fluorescence expression of p-AKT was markedly decreased(P＜0.01),the con-tents of MDA and NO were dramatically enhanced,and the contents of SOD and T-AOC were signifi-cantly downregulated(P＜0.01).The protein expres-sion of p-PI3K/PI3K,p-AKT/AKT,Nrf2 and the mRNA expression of Nrf2,HO-1,GCLM and SOD markedly declined(P＜0.01).Compared with high glucose group,foot process fusion and adhesion of podo-cytes in oxytropis falcata group and oxytropis falca-ta+inhibitor group were improved in varying de-grees,apoptosis rate,migration ability and intracel-lular ROS level significantly declined(P＜0.05,P＜0.01),p-AKT fluorescence expression increased(P＜0.01),NO content decreased,T-AOC level elevated(P＜0.01);the content of MDA decreased and the activity of SOD notably rose(P＜0.01),the protein expression of p-PI3K/PI3K,p-AKT/AKT,Nrf2 and the mRNA expression of Nrf2,HO-1,GCLM and SOD markedly increased in oxytropis falcata group(P＜0.05,P＜0.01);the level of ROS in podocytes im-proved(P＜0.01),the fluorescence expression of p-AKT decreased(P＜0.05),the content of NO upregu-lated,the content of T-AOC downregulated,and the expression of p-PI3K/PI3K,p-AKT/AKT,Nrf2 pro-tein and HO-1,GCLM,SOD mRNA decreased in in-hibitor group(P＜0.05,P＜0.01).Compared with oxy-tropis falcata group,the apoptosis rate,migration ability and intracellular ROS level of podocytes in oxytropis falcata+inhibitor group markedly in-creased(P＜0.05,P＜0.01),p-AKT fluorescence ex-pression declined(P＜0.01),MDA and NO content increased,SOD and T-AOC content decreased(P＜0.05,P＜0.01),p-PI3K/PI3K,p-AKT/AKT,Nrf2 protein and Nrf2,HO-1,GCLM,SOD mRNA expression all dramatically downregulated(P＜0.05,P＜0.01).CON-CLUSION:Oxytropis falcata extract may protect podocytes by activating the PI3K/AKT/Nrf2 signal-ing pathway,thereby improving the morphological,structural and functional changes of podocytes in-duced by high glucose and inhibiting oxidative stress response.

AIM:To investigate the effect of drug-containing serum of oxytropis falcata extract on oxi-dative stress injury of podocyte induced by high glucose through PI3K/AKT/Nrf2 pathway.METH-ODS:The rat renal podocyte was cultured in vitro,and the concentration and time of D-glucose mod-elling and the optimal concentration and time of administration in the drug-containing serum of oxy-tropis falcata extract were screened.The cells were divided into normal group,high glucose group,high glucose+blank serum group,oxytropis falcata group,inhibitor group,oxytropis falcata+inhibitor group.Rhodamine staining and electron microsco-py were used to observe the morphological and pathological changes of podocyte,flow cytometry was used to detect apoptosis rate,and cell migra-tion ability was detected by scratch test.Immuno-fluorescence and fluorescence probe were used to detect the fluorescence expression of p-AKT and ROS level of cells,ELISA was used to detect the con-tent of MDA,NO,SOD and T-AOC in the superna-tant of cells,and Western Blot was used to detect the protein expression of p-PI3K/PI3K,p-AKT/AKT and Nrf2 in cells.The mRNA expressions of Nrf2,HO-1,GCLM and SOD were detected by RT-qPCR.RESULTS:It was selected that 45 mmol/LD-glucose induction for 48 hours was the best modeling con-dition,and the 1-fold dilution of the medicated se-rum of oxytropis falcata extract for 48 hours was the best concentration and intervention time.Com-pared with the normal group,the foot processes of the high glucose group were widely fused and ad-hered to each other,the apoptosis rate,migration ability and intracellular ROS level were significantly increased(P＜0.01),the fluorescence expression of p-AKT was markedly decreased(P＜0.01),the con-tents of MDA and NO were dramatically enhanced,and the contents of SOD and T-AOC were signifi-cantly downregulated(P＜0.01).The protein expres-sion of p-PI3K/PI3K,p-AKT/AKT,Nrf2 and the mRNA expression of Nrf2,HO-1,GCLM and SOD markedly declined(P＜0.01).Compared with high glucose group,foot process fusion and adhesion of podo-cytes in oxytropis falcata group and oxytropis falca-ta+inhibitor group were improved in varying de-grees,apoptosis rate,migration ability and intracel-lular ROS level significantly declined(P＜0.05,P＜0.01),p-AKT fluorescence expression increased(P＜0.01),NO content decreased,T-AOC level elevated(P＜0.01);the content of MDA decreased and the activity of SOD notably rose(P＜0.01),the protein expression of p-PI3K/PI3K,p-AKT/AKT,Nrf2 and the mRNA expression of Nrf2,HO-1,GCLM and SOD markedly increased in oxytropis falcata group(P＜0.05,P＜0.01);the level of ROS in podocytes im-proved(P＜0.01),the fluorescence expression of p-AKT decreased(P＜0.05),the content of NO upregu-lated,the content of T-AOC downregulated,and the expression of p-PI3K/PI3K,p-AKT/AKT,Nrf2 pro-tein and HO-1,GCLM,SOD mRNA decreased in in-hibitor group(P＜0.05,P＜0.01).Compared with oxy-tropis falcata group,the apoptosis rate,migration ability and intracellular ROS level of podocytes in oxytropis falcata+inhibitor group markedly in-creased(P＜0.05,P＜0.01),p-AKT fluorescence ex-pression declined(P＜0.01),MDA and NO content increased,SOD and T-AOC content decreased(P＜0.05,P＜0.01),p-PI3K/PI3K,p-AKT/AKT,Nrf2 protein and Nrf2,HO-1,GCLM,SOD mRNA expression all dramatically downregulated(P＜0.05,P＜0.01).CON-CLUSION:Oxytropis falcata extract may protect podocytes by activating the PI3K/AKT/Nrf2 signal-ing pathway,thereby improving the morphological,structural and functional changes of podocytes in-duced by high glucose and inhibiting oxidative stress response.

Diabetic kidney disease （DKD） is one of the typical microvascular complications in patients with diabetes and a major cause of end-stage renal disease， with the pathogenesis remains to be elucidated. It may be associated with hemodynamic effects， genetic factors， kidney inflammatory injury， oxidative stress， autophagy dysregulation， metabolic disorders and so on. Because of its complex mechanism， there are no specific prevention and treatment measures in clinical practice. AMP-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway is a classical pathway involved in the regulation of autophagy. This pathway can be activated for treating DKD. Recent studies have demonstrated that the active components in Chinese medicinal herbs play a role in the prevention and treatment of DKD by directly acting on targeted cells and autophagy targets， which has attracted extensive attention. Researchers have extensively studied the occurrence and development of DKD and the mechanism of drug intervention in DKD， and the results prove that AMPK/mTOR pathway plays a role in the development of this disease. The active components in Chinese medicinal herbs regulate the AMPK/mTOR signaling pathway to affect autophagy， alleviate oxidative stress， inflammation， and extracellular matrix aggregation， and promote the generation of autophagosomes， thus mitigating kidney injury. This paper mainly reviews the relationship between AMPK/mTOR signaling pathway， autophagy， and DKD and the mechanism of active components in Chinese medicinal herbs in mediating autophagy via the AMPK/mTOR pathway， aiming to provide a theoretical basis for the clinical prevention and treatment of DKD.