Exploration on the Protective Effects and Mechanisms of Modified Shenqi Dihuang Decoction on Podocytes in db/db Mice Based on ROS/NLRP3/GSDMD Signaling Pathway
10.19879/j.cnki.1005-5304.202502579
- VernacularTitle:基于ROS/NLRP3/GSDMD信号通路探讨参芪地黄汤化裁方对db/db小鼠足细胞的保护作用及机制
- Author:
Guiyan SUN
1
;
Mingzhe LI
;
Yan SHI
;
Xiaoyan ZHUANG
;
Xiaonan DUAN
;
Moyan ZHANG
;
Zhihan LEI
;
Chunhui ZHANG
;
Guanqi YANG
;
Yufeng YANG
;
Jing LYU
Author Information
1. 辽宁中医药大学,辽宁 沈阳 110847;辽宁省糖尿病中医病证结合重点实验室,辽宁 沈阳 110847;辽宁中医药大学附属医院,辽宁 沈阳 110000
- Publication Type:Journal Article
- Keywords:
diabetes kidney disease;
pyroptosis;
modified Shenqi Dihuang Decoction;
NLRP3;
mice
- From:
Chinese Journal of Information on Traditional Chinese Medicine
2025;32(11):123-132
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the protective effect and possible mechanism of modified Shenqi Dihuang Decoction on podocytes in db/db mice based on ROS/NLRP3/GSDMD signaling pathway.Methods Fifty 8-week-old male db/db mice(SPF grade)were randomly divided into the model group,losartan group and TCM low-,medium-and high-dosage groups,with 10 mice in each group.Ten heterozygous db/m mice served as the blank group.Interventions were administered respectively for 12 weeks.The body mass,random blood glucose,serum creatinine,blood urea nitrogen and 24 h urinary protein content were detected,HE,PAS,PASM,Masson and Sirius red staining was used to observe the morphology of renal tissue,transmission electron microscopy was used to observe the ultrastructure of renal tissue,fluorescent probes were used to observe the release of ROS in renal tissue,immunofluorescence staining was used to detect the expression of Nephrin,NLRP3,Cleaved Caspase-1 and GSDMD-N in renal tissue,and Western blot was used to detect the expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18,Nephrin,Podocin,PODXL,WT-1 and Desmin proteins.Results Compared with the blank group,the body mass and random blood glucose of the model group mice significantly increased(P<0.05),and the contents of serum creatinine,blood urea nitrogen and 24 h urinary protein were significantly increased(P<0.05);glomerular hypertrophy,dilation of renal glomeruli and tubules,thickening of basement membrane,matrix proliferation in mesangial area,abnormal deposition of collagen fibers in renal interstitium,accompanied by damage to renal tubular epithelial structure and focal glomerulosclerosis,significant increase in type Ⅰ collagen deposition,extensive fusion of podocyte processes,and scattered electron dense material in the basement membrane or subepithelial layer;the ROS content in renal tissue significantly increased(P<0.05),and the protein expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18 and Desmin significantly increased(P<0.05),the protein expression of Nephrin,Podocin,PODXL and WT1 significantly decreased(P<0.05).Compared with the model group,the body mass and random blood glucose of mice in each dosage of TCM group were relatively stable,the contents of serum creatinine,blood urea nitrogen and 24 h urinary protein decreased;the pathological damage to renal tissue was reduced,the ultrastructure of podocytes was improved,and the density of podocytes increased;the ROS content decreased,and the protein expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18 and Desmin decreased,while the protein expression of Nephrin,Podocin,WT1 and PODXL increased.With the dosage of modified Shenqi Dihuang Decoction increased,the improvement effect gradually strengthened,and the differences in TCM high-dose group was statistically significant(P<0.05).Conclusion Modified Shenqi Dihuang Decoction can protects podocytes in db/db mice,potentially by modulating the ROS/NLRP3/GSDMD signaling pathway.
