Introduction: Renal ischemia-reperfusion injury (IRI) is an integral process in renal transplantation, which results in compromised graft survival. Macrophages play an important role in both the early inflammatory period and late fibrotic period in response to IRI. In this study, we investigated whether scutellarin (SCU) could protect against renal IRI by regulating macrophage polarization.
Method: Mice were given SCU (5-50 mg/kg) by gavage 1 hour earlier, followed by a unilateral renal IRI. Renal function and pathological injury were assessed 24 hours after reperfusion. Apoptosis and macrophage polarization in vivo was evaluated with pathological staining, western blot (WB), PCR and ELISA. In vitro experiment, RAW 264.7 cells and primary bone marrow derived macrophages (BMDMs) were used to explore the effect of SCU towards macrophage polarization by WB, PCR, flow cytometry and ELISA. Finally, we explored the effect of SCU on the activation of MAPK pathway in vivo and in vitro.
Results: Administration of 50 mg/kg SCU significantly improved renal function and pathological damage in IRI mice. In addition, SCU alleviated IRI-induced apoptosis. In vivo, it reduced macrophage infiltration and inhibited M1 macrophage polarization. In vitro, 150 μM SCU inhibited M1 polarization of RAW264.7 cells and BMDMs induced by LPS and IFN-γ. Furthermore, both in vivo and in vitro experiments demonstrated that SCU could suppress the activation of the mitogen-activated protein kinase (MAPK) pathway, including extracellular-signal regulated kinase (ERK), jun N-terminal kinase (JNK) and p38/MAPK pathway.
Conclusion: Theses data demonstrated that SCU protects the kidney against IRI by inhibiting macrophage infiltration and polarization towards M1 via the MAPK pathway, suggesting that SCU may be therapeutically important in treatment of IRI.