促红细胞生成素在大鼠肺缺血/再灌注损伤中的作用  

The effect of erythropoietin on the lung ischemia/reperfusion injury in rats

作　　者：金晓盛[1] 李国平[1] 郑继生[1] 许先荣[1] JIN Xiaosheng;LI Guoping;ZHENG Jisheng;XU Xianrong(Pulmonary and Critical Care Medicine,Tongde Hospital of Zhejiang Province,Hangzhou 310000,China)

机构地区：[1]浙江省立同德医院呼吸与危重症医学科,浙江杭州310000

出　　处：《温州医科大学学报》2024年第5期378-383,共6页Journal of Wenzhou Medical University

基　　金：浙江省基础公益研究计划项目(LGF22H010015)。

摘　　要：目的:探讨促红细胞生成素(EPO)在肺缺血/再灌注损伤(LIRI)中的作用及其机制。方法:健康雄性成年SD大鼠40只,随机分成5组(n=8),即对照组、EPO单给药组(3000 U/kg)、LIRI模型组、LIRI模型+EPO预防组(3000 U/kg)(EPO预防组)、LIRI模型+EPO治疗组(3000 U/kg)(EPO治疗组)。RT-qPCR法测定Bcl-2、Bax和caspase-3 mRNA的表达;TUNEL法检测肺细胞凋亡情况;免疫组织化学法测定肺组织中FGF23的表达水平;Western blot检测FGF23、FGFR4、p-ERK1/2蛋白的表达水平;光镜下观察肺组织的病理变化。结果:与对照组比较,模型组Bax、caspase-3 mRNA表达上调(P<0.01),而Bcl-2、FGF23和FGFR4、p-ERK1/2 mRNA表达下降(P<0.01),肺组织损伤和细胞凋亡加重;EPO预防组和EPO治疗组与模型组比较,Bax、caspase-3 mRNA表达下降(P<0.01),而Bcl-2、FGF23和FGFR4、p-ERK1/2 mRNA表达上调(P<0.01),肺组织损伤和细胞凋亡减轻。结论:EPO能减轻LIRI,其机制可能通过FGF23/FGFR4/p-ERK1/2信号通路,上调凋亡抑制因子Bcl-2的表达,下调促凋亡基因Bax、caspase-3的表达,改善其结构破坏和细胞凋亡。Objective:To explore the role and mechanism of erythropoietin(EPO)on lung ischemia/reperfusion injury(LIRI).Methods:Adult male Sprague-Dawley rats were randomly divided into 5 groups(n=8):Control group,EPO single administration group(3000 U/kg),LIRI Model group,LIRI model+EPO pretreatment group(3000 U/kg)(EPO pretreatment group),LIRI model+EPO treatment group(3000 U/kg)(EPO treatment group).The mRNA expression of Bcl-2,Bax and caspase-3 was measured by RT-qPCR.The pneumocyte apoptosis was achieved by TUNEL method.The level of FGF23 in lung tissues was determined by immunohistochemistry.The protein levels of FGF23,FGFR4 and p-ERK1/2 was detected by Western blot.The morphology of lung tissue was observed under the ordinary light microscope.Results:Compared with the control group,the expression of Bax and caspase-3 of LIRI model group had a significant increase(P<0.01),while the Bcl-2,FGF23,FGFR4 and p-ERK1/2 expression levels significantly decreased(P<0.01),and the lung tissue injury and cell apoptosis were aggravated.Compared with LIRI model group,the expression of Bax and caspase-3 of EPO pretreatment group and EPO treatment group was significantly decreased(P<0.01),while the Bcl-2,FGF23,FGFR4 and p-ERK1/2 expression levels significantly increased(P<0.01),and the lung tissue injury and cell apoptosis were reduced.Conclusion:Erythropoietin can effectively improve the lung ischemia/reperfusion injury,which may be related to the activation of the FGF23/FGFR4/p-ERK1/2 signaling pathway,up-regulating the expression of apoptosis inhibitor Bcl-2 while down-regulating the expression of pro-apoptotic genes Bax and caspase-3.

关 键 词：促红细胞生成素 肺 缺血/再灌注损伤 细胞凋亡 FGF23/FGFR4/p-ERK1/2 

分 类 号：R563[医药卫生—呼吸系统]