Tangshenping granule inhibits pyroptosis in a rat model of streptozotocin-induced diabetic nephropathy via the NLRP3/caspase-1/GSDMD pathway
- Author:
Gao KUN
1
;
Zheng PENGFEI
;
Yang TAO
;
Zhang XINXUE
;
Zhao ZONGJIANG
Author Information
1. School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing,102488,China
- Keywords:
Tangshenping;
Pyroptosis;
Diabetic nephropathy;
Streptozotocin
- From:
Journal of Traditional Chinese Medical Sciences
2021;8(4):317-326
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the inhibitory effect of Tangshenping (TSP) on pyroptosis in a streptozotocin-induced diabetic nephropathy (DN) rat model.Methods:DN was established in Sprague-Dawley rats.Rats were randomly divided into DN (model group),irbesartan,and TSP low-,medium-,and high-dose groups,besides the control group.The 24 h albuminuria content,and serum content of TC,TGs,Scr,IL-1β,UREA,LDLs,and IL-18 were assessed.Hematoxylin & eosin and Mallory staining were performed to examine pathological changes in the kidney.The mRNA and protein expression of NLRP3,caspase 1,and GSDMD in the kidney were also examined.Results:The 24 h albuminuria content was obviously lower in the treatment groups compared to the model group (all P <.01).Levels of TC,TGs,Scr,UREA,LDLs,and IL-18 after drug interventions were obviously lower compared to the model group (all P <.05).The serum content of IL-1β in the TSP me-dium-and high-dose groups were much lower compared to the model group (P =.013 and P =.001,respectively).Through immunohistochemistry and western blotting,we observed that the protein ex-pressions of NLRP3,caspase-1,GSDMD,IL-1 β,and IL-18 were lower after drug interventions compared to the model group (all P <.05).Using qPCR,we observed that the mRNA expressions of caspase-1,IL-1β,IL-18,and GSDMD after drug interventions were significantly lower compared to the model group (all P <.05).The mRNA expressions of NLRP3 in the TSP medium-and high-dose groups were both lower compared to the model group (all P <.05).Conclusion:TSP downregulated mRNA and protein expressions of NLRP3,caspase-1,and GSDMD.Our findings demonstrate that the beneficial effects of TSP on renal function are at least partly mediated by the inhibition of micro-inflammation and modulation of the expression of pyroptosis-related factors.