目的 研究罗沙司他对腹膜纤维化的影响.方法 采用5.6 mmol/L葡萄糖溶液(N组)、138 mmol/L葡萄糖溶液(C组)、138 mmol/L葡萄糖溶液联合5 μmol/L罗沙司他(R组)培养人腹膜间皮细胞(HPMCs);选取24只同一批次8～10周龄的SD成年雄性大鼠作为研究对象.腹腔注射4.25％高糖腹透液建立大鼠腹膜纤维化模型,分为正常组(RN组)、模型组(RC组)、罗沙司他常规剂量组(RR-N组)和罗沙司他高剂量组(RR-H组).观察腹膜组织形态,检测低氧诱导因子-1α(HIF-1α)、1型胶原蛋白(Col-1)、血管内皮生长因子(VEGF)、E-钙粘蛋白(E-cad)的表达情况.结果 与N组细胞比较,C组和R组HPMCs中HIF-1α、Col-1、VEGF表达增高,E-cad表达减少(P＜0.05);与C组比较,R组的HIF-1α、Col-1、VEGF表达增高,E-cad表达减少(P＜0.05).与RN组大鼠比较,RC组大鼠腹膜结构紊乱,大量胶原纤维沉积,致密层增厚;RR-N、RR-H组大鼠血管增生明显,但致密层厚度与RC组无明显差异;与RN比较,RC组腹膜组织HIF-1α、Col-1、VEGF表达增高,E-cad表达减少(P＜0.05);与RC组比较,RR-N组HIF-1α、Col-1、VEGF、E-cad表达无明显差异;与RC组及RR-N组比较,RR-H组腹膜组织HIF-1α、VEGF表达增高,E-cad表达减少,差异有统计学意义(P＜0.05).结论 罗沙司他可以引起腹膜细胞HIF-1α表达增高,增加纤维化信号蛋白表达;常规剂量罗沙司他不增加大鼠腹膜组织纤维化,而大剂量的罗沙司他可能存在增加腹膜纤维化的风险.
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.
肖伍豪;黄意雄;钟玮;刘抗寒
湖南省人民医院/湖南师范大学附属第一医院肾内科,长沙 410005
临床医学
罗沙司他;缺氧诱导因子;腹膜透析;腹膜纤维化
roxadustat;hypoxia-inducible factor;peritoneal dialysis;peritoneal fibrosis
《重庆医学》 2024 (013)
1927-1934,1940 / 9
湖南省卫生健康委员会科研计划项目(202103051068);湖南省中医药管理局项目(2021102).
10.3969/j.issn.1671-8348.2024.13.002
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