重庆医学2024,Vol.53Issue(13):1927-1934,1940,9.DOI:10.3969/j.issn.1671-8348.2024.13.002
罗沙司他对腹膜纤维化的影响研究
Study on effect of roxadustat on peritoneal fibrosis
摘要
Abstract
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.关键词
罗沙司他/缺氧诱导因子/腹膜透析/腹膜纤维化Key words
roxadustat/hypoxia-inducible factor/peritoneal dialysis/peritoneal fibrosis分类
医药卫生引用本文复制引用
肖伍豪,黄意雄,钟玮,刘抗寒..罗沙司他对腹膜纤维化的影响研究[J].重庆医学,2024,53(13):1927-1934,1940,9.基金项目
湖南省卫生健康委员会科研计划项目(202103051068) (202103051068)
湖南省中医药管理局项目(2021102). (2021102)