*Purpose: miR-223 is a well-studied miRNA that has been tested for abnormal expression in many diseases, and it has been found to play a regulatory role in I/R injury. Therefore, in this study, we used BALB/c mice to construct a model of renal I/R injury to explore the regulatory role of miR-223 in renal I/R injury.

*Methods: In this study, we demonstrated that apoptosis plays a role in the mechanism of renal I/R injury in vitro and in vivo. By co-culturing MSCs with TCMK-1 cells in vitro, we know that MSCs have a protective effect on renal I/R injury, and the protective effect depends on exosomes. At the same time, by constructing mouse kidney I/R injury model, we also confirmed the protective effect of MSCs-derived exosomes on renal I/R injury in mice. We further explored the protective mechanism of miR-223 in exosomes on renal I/R injury.

*Results: In experiments both in vitro and vivo, we overexpressed miR-223 in exosomes. Compared with the model group and the normal exosomes group, overexpression of miR-223 significantly reduced the expression of caspase1, NLRP3, and Gasdermin⁃N, and decreased the inflammatory factors IL⁃1β and IL⁃18. When miR-223 was knocked down, the ability to reduce the expression of related proteins and inflammatory factors was significantlyimpaired. Through luciferase reporter assay, we confirmed that miR-223 can target NLRP3 and affect its protein expression. The results in TCMK-1 cells also confirmed this conclusion. These results suggest that miR-223 in MSCs-derived exosomes targets NLPR3 to inhibit pyroptosis pathway, reduce the expression of related inflammatory factors, and protect against renal I/R injury.

*Conclusions: Taken together, our study found that miR-223 in MSCs-derived exosomes targets NLPR3 to inhibit pyroptosis pathway, reduce the expression of related inflammatory factors, and protect against renal I/R injury.

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