To explore the kidney yang deficiency pattern (KYDP) in a chronic kidney disease (CKD) rat model and the mechanisms underlying the effects of Zhenwu decoction (ZWD) by conducting transcriptomic and metabolomic analyses.

Adriamycin (ADR) combined with hydrocortisone (HC) was used to induce CKD with KYDP in rats. ADR was injected into the tail vein twice. HC was injected intramuscularly for 8 weeks. ZWD was administered by gavage for 8 weeks. The general condition was observed, 24-h urine protein was detected, serum corticosterone, triiodothyronine, thyroxine, TSH, testosterone, cAMP, and cGMP levels were determined, and pathological analysis was conducted. Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes (DEGs), differentially expressed metabolites (DEMs), and differentially expressed pathways (DEPs). The core DEMs and DEGs were input to Metaboanalyst 5.0 to identify the pathways affected by ZWD.

In the HC group, KYDP symptoms were observed. Compared with control group, the levels of 24-h urine protein, TSH, and cGMP significantly increased (all P < .01), and corticosterone, triiodothyronine, thyroxine, and cAMP significantly decreased (all P < .01) in the HC group. After ZWD intervention, the levels of above-mentioned indicators could be reversed to some extent. Pathological analysis in the HC group revealed kidney lesions. DEGs in the ZWD group were mainly associated with pathways such as nucleotide synthesis and endocrine pathways. In the ZWD group, differences in biosynthesis of unsaturated fatty acids and butanoate metabolism were observed. The following pathways were significantly affected by ZWD: arachidonic acid metabolism, valine, leucine, and isoleucine biosynthesis, linoleic acid metabolism, and alpha-linolenic acid metabolism.

ZWD can be used to treat KYDP in CKD through regulating arachidonic acid metabolism, valine, leucine, and isoleucine biosynthesis, linoleic acid metabolism, and alpha-linolenic acid metabolism.

To explore the inhibitory effect of Tangshenping (TSP) on pyroptosis in a streptozotocin-induced diabetic nephropathy (DN) rat model.

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.

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).

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.