PTH-HIF1α-EPO信号通路促进慢性肾病患者肾性贫血的机制  

PTH-HIF1α-EPO signaling pathway promotes the pathogenesis of renal anemia in patients with chronic kidney disease

作　　者：吴勐 刘莲芝 邓金秀 钟少榕 丘昭文 章宇 林冲云 WU Meng;LIU Lianzhi;DENG Jinxiu;ZHONG Shaorong;QIU Zhaowen;ZHANG Yu;LIN Chongyun(Department of Nephrology,Longyan First Affiliated Hospital of Fujian Medical University,Longyan 364000,Fujian,China)

机构地区：[1]福建医科大学附属龙岩第一医院肾内科,福建龙岩364000

出　　处：《贵州医科大学学报》2024年第10期1484-1489,共6页Journal of Guizhou Medical University

基　　金：福建省自然科学基金(2020J011324)。

摘　　要：目的探讨甲状旁腺激素(PTH)-低氧诱导因1α(HIF1α)-红细胞生成素(EPO)信号通路在促进慢性肾脏病(CKD)肾性贫血中的作用机制。方法12只6~8周龄的C57BL/6雄性小鼠随机均分为健康小鼠(对照)组及CKD小鼠(CKD模型)组,CKD小鼠组采用5/6肾切除法构建CKD模型,1周后再随机均分为两组、分别腹腔注射磷酸盐缓冲液(PBS)和Deferoxamine;4周后收集各组小鼠血液和肾脏标本,检测小鼠红细胞计数、血红蛋白、血肌酐、尿素氮、尿酸及PTH含量,聚合酶链反应(PCR)检测肾脏组织HIF1α及EPO mRNA表达水平,蛋白印迹法检测肾脏组织热休克蛋白90(HSP90)及Rho相关卷曲螺旋结构蛋白激酶1(ROCK1)蛋白表达水平。结果与健康小鼠组相比,CKD小鼠组血清尿素氮、肌酐、尿酸、PTH水平增高(P<0.05),红细胞计数及血红蛋白含量下降(P<0.05);CKD小鼠组肾脏组织中HIF1α及EPO mRNA表达水平降低(P<0.05);与注射PBS的CKD小鼠组相比,注射Deferoxamine后的CKD小鼠组红细胞数量及血红蛋白含量升高(P<0.05);与健康小鼠组相比,CKD小鼠组HSP90和ROCK1的蛋白表达水平下降(P<0.05)。结论PTH可能通过调节Ras同源家族成员A(RhoA)-Rock影响HIF1α的表达,PTH-HIF1α-EPO信号通路可能是导致CKD患者肾性贫血发生的机制。Objective To investigate the role of parathyroid hormone(PTH)-hypoxia-inducible factor 1-alpha(HIF1α)-erythropoietin(EPO)signaling pathway in renal anemia in chronic kidney disease(CKD)and its mechanism.Methods welve C57BL/6 male mice aged 6 to 8 weeks were randomly divided into healthy mice(control)group and CKD mice(CKD model)group.CKD group was given 5/6 nephrectomy to establish CKD model,and randomly divided into two subgroups one week later.Two subgroups were intraperitoneally injected with phosphate buffer saline(PBS)and Deferoxamine,respectively.After 4 weeks,blood and kidney samples were collected.Mouse red blood cell counts,hemoglobin,serum creatinine,urea nitrogen,uric acid,and PTH levels were measured.Quantitative polymerase chain reaction(qPCR)was used to detect the mRNA expression levels of HIF1αand EPO in kidney tissues.Western blot was performed to detect the protein expression levels of heat shock protein 90(HSP90)and Rho-associated coiled-coil containing protein kinase 1(ROCK1)in kidney tissues.Results When compared to healthy mice group,CKD mice group had elevated levels of serum urea nitrogen,creatinine,uric acid and PTH(P<0.05),decreased red blood cell counts and hemoglobin levels(P<0.05)and decreased mRNA expression levels of HIF1αand EPO in kidney tissues(P<0.05).When compared to CKD mice group injected with PBS,red blood cell counts and hemoglobin levels in CKD mice group after deferoxamine injection were elevated(P<0.05).Protein expression levels of HSP90 and ROCK1 were significantly decreased in CKD mice group when compared to healthy mice group(P<0.05).Conclusion PTH may influence the expression of HIF1αby regulating the ras homolog family member A(RhoA)-ROCK pathway.PTH-HIF1α-EPO signaling pathway may be the mechanism leading to renal anemia in patients with CKD.

关 键 词：甲状旁腺激素 低氧诱导因1α 促红细胞生成素 慢性肾脏病 肾性贫血 热休克蛋白90 Rho相关卷曲螺旋结构蛋白激酶1 

分 类 号：R582.1[医药卫生—内分泌]