Shenfushu granules attenuate diabetic kidney disease by inhibiting PIK3R1/protein kinase B/heparanase-mediated endothelialmesenchymal transition  

作　　者：Xi-Ding Yang Si-Jia Ma Da-Xiong Xiang Yong-Yu Yang 

机构地区：[1]Department of Pharmacy,The Second Xiangya Hospital of Central South University,Changsha 410011,Hunan Province,China

出　　处：《World Journal of Diabetes》2025年第5期297-316,共20页世界糖尿病杂志(英文)

基　　金：Supported by the Changsha Science and Technology Major Project,No.kh2205035;the Hunan Traditional Chinese Medicine Science and Technology Project,No.2021061;the Natural Science Foundation of Hunan Province,No.2025JJ80080。

摘　　要：BACKGROUND Injury to the glomerular filtration barrier causes diabetic kidney disease(DKD),and glomerular endothelial-mesenchymal transition damages the filtration barrier of glomerular endothelial cells.Shenfushu granules(SFSGs)can treat chronic renal failure;however,their role and mechanism in DKD remain unclear.AIM To investigate the role of SFSGs in delaying DKD progression and their underlying mechanism in a streptozotocin-induced DKD mouse model.METHODS The microalbumin content in the urine and the blood glucose,creatinine,and blood urea nitrogen levels in the serum were measured.The expression and distribution ofα-smooth muscle actin(α-SMA),heparan sulfate(HS)and cluster of differentiation(CD)31 were observed through immunofluorescence or immunohistochemistry.Western blotting was conducted to measure the expression of CD31,α-SMA,PIK3R1,protein kinase B(AKT),phospho-PIK3R1,phospho-AKT,and heparanase-1.Network pharmacology was conducted to screen and identify the core components and targets of SFSGs.Molecular docking and dynamic simulations were performed to evaluate the binding ability of the core components of SFSGs to their core targets.RESULTS Compared with those in the model group,the 24-hour microalbuminuria(188.2±20.1 and 140.4±24.7 vs 323.2±44.4),serum creatinine(79.4±2.6 and 68.7±6.0 vs 110.2±4.8),blood urea nitrogen(14.4±1.1 and 13.1±0.5 vs 19.5±1.1),and renal index(20.3±1.0 and 19.6±0.8 vs 25.3±1.7)were significantly lower in the SFSGs(2.08 and 4.16 g/kg/day extract)-treated DKD mice.SFSGs inhibited the down regulation of CD31 and the upregulation ofα-SMA in the glomerular endothelial cells of DKD mice.Additionally,SFSGs suppressed the decrease in glycocalyx thickness and the expression of its component HS.Network pharmacology revealed that PIK3R1 was the core target of SFSGs.SFSGs markedly downregulate the expression of phospho-PIK3R1,phospho-AKT,and heparanase-1.However,the PIK3R1 agonist abolished the regulatory effect of SFSGs on the expression of CD31,α-SMA,and heparanase-1.C

关 键 词：Diabetic kidney disease Glomerular filtration barrier GLYCOCALYX Shenfushu granules PIK3R1 Heparanase-1 Endothelial-mesenchymal transition 

分 类 号：R285[医药卫生—中药学]