Tangshenping granule inhibits pyroptosis in a rat model of streptozotocin-induced diabetic nephropathy via the NLRP3/caspase-1/GSDMD pathway

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 medium- 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 expressions of NLRP3, caspase-1, GSDMD, IL-1β, 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.

Keywords

• Tangshenping
• Pyroptosis
• Diabetic nephropathy
• Streptozotocin