Abstract
BACKGROUND: Buzhong Yiqi decoction (BZYQ) is a classical traditional Chinese formula that has shown potential in alleviating diabetic nephropathy (DN). However, its underlying mechanisms remain unclear. OBJECTIVE: We aimed to explore the potential targets and mechanisms of action of BZYQ in DN. MATERIALS AND METHODS: A DN rat model was induced using a high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin (STZ), followed by treatment with different doses of BZYQ. Initially, the protective effects of BZYQ on renal tissue were assessed by measuring fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), 24-hour urinary total protein (24h-UTP), urinary albumin (ALB), and serum creatinine (SCr) after administration, along with performing hematoxylin-eosin (HE) staining. Subsequently, transcriptomics and bioinformatics approaches were employed to identify the action targets and potential mechanisms of BZYQ in DN rats. Finally, real-time PCR and Western blot analyses were conducted to validate key targets and mechanisms. RESULTS: We observed significant improvements in renal injury in DN rats treated with medium and high doses of BZYQ. Transcriptomic and bioinformatic analyses identified NLRP3, ASC, caspase- 1, GSDMD, IL-1β, and IL-18 as hub genes, along with differential expression of immune-related transcription factors T-bet and GATA-3 in various transcriptomes. In the validation phase, the mRNA and protein expressions of NLRP3, ASC, caspase-1, GSDMD, IL-18, IL-1β, and T-bet were significantly elevated in the DN rat model group, while GATA-3 mRNA and protein levels were significantly decreased; BZYQ was able to reverse these changes. CONCLUSION: BZYQ has been found to have a protective effect on renal tissue damage in DN rats, potentially related to the inhibition of NLRP3 inflammasome pathway activation and the improvement of Th1/Th2 immune cell balance.