罗沙司他通过活化Nrf2/HO-1信号通路保护腹膜透析患者残余肾功能  

Roxadustat protects residual renal function by up-regulating Nrf2/HO-1 signal pathway in patients undergoing peritoneal dialysis

作　　者：邱杰山 方燊燊 暨利军 徐志勇 李霞[1] 陈静静 QIU Jie-shan;FANG shen-shen;JI Li-jun;XU Zhi-yong;LI Xia;CHEN Jing-jing(Department of Nephrology,Xianju People’s Hospital,Southeast District of Zhejiang Provincial People's Hospital,Xianju 317300,China)

机构地区：[1]仙居县人民医院浙江省人民医院浙东南院区肾脏内科,台州317300

出　　处：《中国血液净化》2025年第3期203-207,共5页Chinese Journal of Blood Purification

基　　金：台州市科技局科研计划项目(23ywb163);浙江省中医药科技计划项目(2023ZL793)。

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)、β_(2)-微球蛋白(β_(2)-microglobulin,β_(2)-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Nrf2 mRNA、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β_(2)-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HO1mRNA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β_(2)-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β_(2)-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β_(2)-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。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),β_(2)-microglobulin(β_(2)-MG),N-acetyl-βglucosamine 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,urinaryβ_(2)-MG,NAG enzyme,RBP and 8-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 Nrf2 mRNA and HO-1 mRNA 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 and 0.040 respectively).After the treatment,RRF was significantly higher in Rox group than in ESA group(t=4.710,P<0.001).Nrf2 mRNA was negatively correlated with urinaryβ_(2)-MG,NAG enzyme,RBP and 8-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 urinaryβ_(2)-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 urinaryβ_(2)-MG,NAG enzyme and RBP(r=0.456,0.453 and 0.639 respectively;P=0.005,=0.005 and<0.001 respectively),and negatively correlated with RRF(r=-0.343,P=0.03

关 键 词：罗沙司他 腹膜透析 Nrf2/HO-1信号通路 残余肾功能 

分 类 号：R459.5[医药卫生—治疗学]