【摘要】 目的 探讨罗沙司他（roxadustat,Rox）对腹膜透析（peritoneal dialysis,PD）患者残余肾功能（residual renal function,RRF）的干预作用及可能的机制。方法 行PD治疗的患者78例，分为红细胞生成素（erythropoiesis stimulating agent,ESA）治疗组（ESA组）和Rox治疗组（Rox组）。检测尿8-羟基脱氧鸟苷酸（8-hydroxydeoxyguanosine,8-OHdG）、β₂-微球蛋白（β₂-microglobulin,β₂-MG）、N-乙酰-β氨基葡萄糖苷（N-acetyl-βglucosaminidase,NAG）酶、视黄醇结合蛋白（retinol binding protein,RBP），血单核细胞核因子E2相关因子2（nuclear factor-erythoid2 related factor-2,Nrf2）mRNA及血红素氧合酶1（heme oxygenase-1,HO-1）mRNA。比较治疗后上述指标的差异，将Nrf2mRNA、HO-1 mRNA表达水平及尿8-OHdG分别与其余指标做相关性分析。结果 治疗后，Rox组尿β₂-MG、NAG酶、RBP及8-OHdG较治疗前下降（t=3.751、2.522、3.292、3.829,P<0.001、0.014、0.002、<0.001），且低于ESA组（t=3.889、1.627、3.694、2.769,P<0.001、0.035、<0.001、P=0.007），而Nrf2 mRNA及HO-1mRNA表达水平较治疗前升高（t=2.797、1.724,P=0.007、0.032），且高于ESA组（t=3.507、2.087,P=0.001、0.040），治疗后ESA组RRF高于ESA组（t=4.710,P<0.001）。Nrf2 mRNA表达水平与尿β₂-MG、NAG酶、RBP及8-OHdG呈负相关（r=-0.617、-0.511、-0.598、-0.591,P<0.001、0.001、<0.001、<0.001），与RRF呈正相关（r=0.579,P<0.001）。HO-1 mRNA表达水平与尿β₂-MG、RBP及8-OHd呈负相关（r=-0.668、-0.406、0.606,P<0.001、0.013、<0.001），与RRF呈正相关（r=0.532,P=0.001）。尿8-OHdG表达水平与尿β₂-MG、NAG酶及RBP表达水平呈正相关（r=0.456、0.453、0.639,P=0.005、0.005、<0.001），与肾小管上皮细胞呈负相关（r=-0.343,P=0.038）。结论 Rox可能通过活化Nrf2/HO-1信号通路，抑制氧化应激反应而减轻PD患者肾小管上皮细胞损伤，进而延缓RRF下降。更多还原

【Abstract】 Objective To investigate the effect of Roxadustat （Rox） on residual renal function （RRF） in patients undergoing peritoneal dialysis （PD） and its possible mechanism.Methods A total of 78 patients undergoing PD were divided into erythropoietin （ESA） treatment group （ESA group） and Rox treatment group（Rox group）.Urinary 8-hydroxydeoxyguanosine （8-OHdG）,β2-microglobulin （β₂-MG）,N-acetyl-β glucosamine glucosidase （NAG） enzyme,retinol binding protein （RBP）,blood Nrf2 mRNA and HO-1 mRNA were measured.These laboratory parameters were compared between the two groups before and after treatment.The correlations of the laboratory parameters with the levels of Nrf2 mRNA,HO-1 mRNA and urinary 8-OHdG were analyzed.Results At the end of follow-up in Rox group,urinary β₂-MG,NAG enzyme,RBP and8-OHdG were significantly lower than those before treatment （t=3.751,2.522,3.292 and 3.829 respectively;P<0.001,=0.014,=0.002 and<0.001 respectively）,and were significantly lower than those in ESA group （t=3.889,1.627,3.694 and 2.769 respectively;P<0.001,=0.035,<0.001 and P=0.007 respectively）;while Nrf2mRNA and HO-1 m RNA were significantly higher than those before the treatment （t=2.797 and 1.724 respectively;P=0.007 and 0.032 respectively） and those in ESA group （t=3.507 and 2.087 respectively,P=0.001 and0.040 respectively）.After the treatment,RRF was significantly higher in Rox group than in ESA group （t=4.710,P<0.001）.Nrf2 m RNA was negatively correlated with urinary β₂-MG,NAG enzyme,RBP and8-OHdG （r=-0.617,-0.511,-0.598 and-0.591 respectively;P<0.001,=0.001,<0.001 and<0.001 respectively）,and positively correlated with RRF （r=0.579,P<0.001）.HO-1 mRNA was negatively correlated with urinary β₂-MG,RBP and 8-OHdG （r=-0.668,-0.406 and 0.606 respectively;P<0.001,=0.013 and<0.001 respectively）,and positively correlated with RRF （r=0.532,P=0.001）.Urinary 8-OHdG was positively correlated with urinary β₂-MG,NAG enzyme and RBP （r=0.456,0.453 and 0.639 respectively;P=0.005,=0.005and<0.001 respectively）,and negatively correlated with RRF （r=-0.343,P=0.038）.Conclusion Rox may alleviate the damage of renal tubular epithelial cells and protect RRF in PD patients by activating Nrf2/HO-1signal pathway and inhibiting oxidative stress reaction.更多还原