Study on effect of roxadustat on peritoneal fibrosis
Objective To study the effect of roxadustat on peritoneal fibrosis.Methods The human peritoneal mesothelial cells(HPMCs)were cultured with 5.6 mmol/L(N group),138 mmol/L(C group)or 138 mmol/L glucose solution combined with 5 μmol/L roxadustat(R group).A total of 24 SD adult male rats aged 8-10 weeks from the same batch were selected as the study subjects.4.25％high-glucose peritoneal di-alysis solution was intraperitoneally injected to construct the rat peritoneal fibrosis model,which was divided into the normal group(RN group),model group(RC group),roxadustat conventional dose group(RR-N group)and roxadustat high-dose group(RR-H group).The morphology of peritoneal tissues was observed,and the expression levels of HIF-1α,Col-1,VEGF and E-cadherin were detected.Results Compared with the group N,the expression levels of HIF-1α,Col-1 and VEGF in HPMCs in the group C and group R were increased and the expression level of E-cad was decreased(P＜0.05);compared with the group C,the expression levels of HIF-1α,Col-1 and VEGF in the group R were increased and the expression level of E-cad was decreased(P＜0.05).Com-pared with the RN group,the peritoneal structure in the group RC was disordered,a large number of collagen fibers were deposited,and the dense layer was thickened;the angiogenesis in the RR-N group and RR-H group was obvious,but there was no significant difference in the thickness of the dense layer compared with the RC group;compared with the RN group,the expression levels of HIF-1α,Col-1 and VEGF in the peritoneal tissue of the group RC were increased,and the expression level of E-cad was decreased(P＜0.05);compared with the group RC,the expression levels of HIF-1α,Col-1,VEGF and E-cad in the RR-N group had no significant difference;compared with the group RC group and RR-N group,the expression levels of HIF-1α and VEGF in peritoneal tissue in the RR-H group were increased,the expression level of E-cad was decreased,and the differences were statistically significant(P＜0.05).Conclusion Roxadustat could cause an increase of HIF-1αexpression level in peritoneal cells and increase the expression level of fibrosis signaling proteins;while con-ventional dose roxadustat does not increase the peritoneal tissue fibrosis in rats,while high-dose roxadustat may have the risk of aggravating peritoneal fibrosis.
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