Abstract: Objective To investigate the role of chemokine receptor 2 (CCR2) inhibitor RS504393 in alleviating renal interstitial fibrosis and the underlying mechanisms in unilateral ureteral obstruction mouse model. Methods Mice were divided into three groups randomly: sham group，model group，and administration group. The unilateral ureter separation was performed in mice of the sham group, and mice in the other two groups underwent unilateral ureteral obstruction (UUO) to induce renal interstitial fibrosis. Three days before UUO, the mice in the administration group were administered with RS504393 orally twice a day at a dose of 25 mg /kg for 17 consecutive days. Masson and HE staining were used to determine the degree of renal fibrosis and the inflammatory cells infiltration. Flow cytometry analysis was used to determine the proportion of CCR2 and CD11b+Ly6C+ monocytes. Results Compared with sham group, the degree of renal fibrosis was significantly increased in model group (P<0.05). Renal fibrosis was alleviated in the administration group compared to model group (P<0.05)；Compared with sham group, the infiltration of inflammatory cells was increased in model group (P<0.05), compared with model group, the infiltration of inflammatory cells reduced in the administration group (P<0.05); The percentage of CCR2 and CD11b+Ly6C+ monocytes was increased in model group compared to sham group. Compared with model group, CCR2 and CD11b+Ly6C+ inflammatory monocytes were also reduced in the administration group (P<0.05). Conclusions CCR2 inhibitor RS504393 alleviate renal fibrosis by reducing CD11b+Ly6C+ monocyte infiltration.

Key words: Renal fibrosis, Chemokine receptor 2, CD11b+Ly6C+ monocytes