*Purpose: Investigate the underlying mechanism of mesenchymal stem cells (MSCs) on protection of renal ischemia reperfusion injury (IRI) .

*Methods: Exosomes originated from MSCs (MSC-ex) were extracted according to the instructions of Total Exosome Isolation Reagent. Rats were divided into five groups: sham-operated, IRI, MSC, MSC-ex, and MSC-ex + RNAase group. MSCs or MSC-ex were injected via carotid artery. The renal function test and pathological detection were applied to determine the renoprotection of MSC-ex on IRI. Western blotting and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were conducted to examine the levels of apoptosis-related proteins and inflammatory cytokines.

*Results: MSC-derived exosomes attenuated renal dysfunction, histologic damage, and decreased apoptosis. The expression levels of inflammatory cytokines, such as interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), and interferon gamma (IFN-γ), were decreased by the MSC-ex treatment. The expression levels of caspase-9, cleaved caspase-3, Bax, and Bcl-2 caused by IR were also inhibited by MSC-ex. MSC-ex +RNAase group shared the similar pattern of changes with IRI group, likely due to the ability of RNA hydrolase to eliminate the function of exosomes.

*Conclusions: Exosomes originating from MSCs have protective effects on IRI via inhibiting cell apoptosis and inflammatory responses. Out findings may provide a new insight into therapeutic mechanism of MSCs on renal IRI.

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