Huoxue Jiedu Huayu Formula Alleviates Cell Pyroptosis in Contralateral Kidneys of 6-Month-Old UUO Rats through the NLRP3/Caspase-1/IL-1β Pathway

Abstract

Objectives. To study the protective effects and mechanisms of Huoxue Jiedu Huayu formula on cell pyroptosis through the NLRP3/caspase-1/IL-1β pathway in contralateral kidneys in 6-month-old unilateral ureteral obstruction (UUO) rats. Methods. Wistar rats were randomly assigned to 5 groups: a Sham group, a unilateral nephrectomy group (UNX group), a UUO group, a UUO treated with spironolactone group (Spi group), and a UUO treated with Huoxue Jiedu Huayu formula group (HJHF group). After 6 months of oral drug intervention, blood and contralateral kidneys were collected for research. Results. The morphology and function of the contralateral kidneys were essentially normal after unilateral nephrectomy. HJHF obviously decreased serum creatinine, urea, and inflammatory lesions and depressed cell pyroptosis based on the NLRP3/caspase-1/IL-1β pathway. Moreover, spironolactone, a mineralocorticoid receptor (MR) blocker, suppressed cell pyroptosis through SGK-1 and NF-кB. Conclusion. HJHF and spirolactone inhibited excessive activation of MR and then reduced cell pyroptosis, which was dependent on the NLRP3/caspase-1/IL-1β pathway, to protect the contralateral kidneys of 6-month-old UUO rats.

The Role of Pyroptosis in the Pathogenesis of Kidney Diseases

“…Disulfiram, a drug used to treat alcohol addiction and a pore-formation inhibitor of GSDMD, alleviated inflammation and fibrosis in a rat UUO model by inhibiting GSDMD cleavage and pyroptosis [ 101 ]. Huoxue Jiedu Huayu formula prevented the development of pyroptosis by downregulating NLRP3/caspase-1/IL-1β pathway in UUO rats [ 102 ]. Suyin Detoxification Granule inhibited NLRP3-mediated pyroptosis during renal fibrosis [ 103 ].…”