OBJECTIVE To explore the regulatory effects of Buqi tongqiao formula on intestinal flora and immune balance in immunoglobulin A nephropathy （IgAN） rats based on the theory of “treating different diseases with the same therapy”. METHODS Male SD rats were randomly assigned to the Normal group and the modeling group. IgAN rat models were established in the modeling group by intragastric administration of bovine serum albumin， subcutaneous injection of carbon tetrachloride and castor oil mixture， and tail vein injection of lipopolysaccharide. Successfully modeled rats were then randomly divided into the model group （Model group）， Buqi tongqiao formula low-dose group （BQTQ-L group）， Buqi tongqiao formula high-dose group （BQTQ- H group）， and positive control group （BZP group）， with 15 rats in each group. BZP group received intragastric administration of benazepril hydrochloride （10 mg/kg）， while BQTQ-L and BQTQ-H groups were given Buqi tongqiao formula at doses of 9.81 and 19.62 g/kg （calculated as raw herb weight）， respectively. The Normal group and the Model group received an equal volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The 24-hour urinary total protein （24 h UTP） contents were measured at weeks 8， 10， 12， 14 and 16 of the experiment. After the last administration， serum creatinine （Scr） and blood urea nitrogen （BUN） contents were detected. Renal histopathological changes and glomerular IgA immune complex deposition were examined. Additionally， alterations in gut microbiota composition， the proportions of peripheral T helper cell 17 （Th17） and regulatory T cell （Treg）， as well as the ratio of Th17 and Treg （Th17/Treg）， were analyzed across all groups. RESULTS Compared with the Model group， rats in both BQTQ-L and BQTQ-H groups showed alleviated mesangial cell hyperplasia， reduced matrix expansion， and decreased IgA immune complex deposition in the glomeruli. The 24 h UTP contents （at weeks 14 and 16 in the BQTQ-L group； at weeks 12， 14 and 16 in the BQTQ-H group）， Scr and BUN contents， IgA-positive area fluorescence intensities， relative abundances of Firmicutes， Th17 cell proportions， and Th17/Treg were significantly decreased in both BQTQ-L and BQTQ-H groups （P＜0.05）； while the Chao1， Observed species， Shannon， and Simpson （except for BQTQ-H group） indexes， the relative abundances of Bacteroidota， and the proportions of Treg were significantly increased （P＜0.05）. Differential microbiota included c_Clostridia （BQTQ-L group vs. Model group） and g_Ruminococcus （BQTQ-H group vs. Model group）， etc. CONCLUSIONS Buqi tongqiao formula may alleviate renal injury and exert a renal protective effect in IgAN rats by modulating intestinal flora homeostasis and Th17/Treg immune balance.

As a novel star molecule, gasdermin D (GSDMD) plays an important role in the amplification of immune inflammatory response and the process of pyroptosis. After being cleaved and activated by caspase-1, the N-terminal of GSDMD is rapidly released, which anchors on the cell membrane and forms pores, thereby leading to pyroptosis, accompanied by the release of a large amount of the strong proinflammatory factors IL-1β and IL-18. Acute/chronic liver inflammatory response and cell death are the common pathological features of liver diseases such as viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune liver disease, liver failure, and hepatocellular carcinoma. This article summarizes the basic structural characteristics of GSDMD and elaborates on its important role in the pathological progression of various liver diseases. In addition, it is proposed that prevention and treatment strategies with GSDMD as a potential therapeutic target can provide new ideas for further studies on the clinical prevention and treatment of liver diseases.