血管紧张素Ⅱ受体样1受体内源性配体13、血管紧张素Ⅱ在自体动静脉内瘘狭窄中的表达及机制研究  

Study on the expression and activity of Apelin-13 and angiotensinⅡin autologous arteriovenous fistula stenosis

作　　者：周青溢 徐玉祥 王科峰[2] 冀倩倩 ZHOU Qing-yi;XU Yu-xiang;WANG Ke-feng;JI Qian-qian(Department of Nephrology,Xidian Group Hospital,Xi'an 710077,China;Department of Renal Endocrinology,The Second Affiliated Hospital of Xi'an Medical College,Xi’an 710038,China;Department of Nephropathy,The Third People's Hospital of Hubei Province,Wuhan 430030,China)

机构地区：[1]西电集团医院肾内科,西安710077 [2]西安医学院第二附属医院肾脏内分泌科,西安710038 [3]湖北省第三人民医院肾病内科,武汉430030

出　　处：《中国血液净化》2022年第2期107-110,共4页Chinese Journal of Blood Purification

基　　金：陕西省教育厅科研计划项目(13JK0776)。

摘　　要：目的研究血管紧张素Ⅱ受体样1受体内源性配体13(angiotensin Ⅱ receptor-like 1 endogenous ligand 13,Apelin-13)、血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)在自体动静脉内瘘(autogenous arteriovenous fistula,AVF)狭窄中的表达及机制。方法选取血液透析患者90例,根据是否发生AVF狭窄分为狭窄组和正常组,各45例。选取同期入院的慢性肾脏病患者45例,作为对照组。比较3组的Apelin-13、AngⅡ、一氧化氮(nitric oxide,NO)水平,分析AVF狭窄患者Apelin-13、AngⅡ与NO水平的相关性,使用ROC曲线分析Apelin-13、AngⅡ对AVF狭窄的诊断价值。将人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)分别经AngⅡ(A组)、Apelin-13(B组)以及AngⅡ联合Apelin-13(C组)刺激后,分析NO、磷酸化内皮型一氧化氮合酶(phosphorylated endothelial nitric oxide synthase,peNOS),内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)的表达情况。结果狭窄组、正常组和对照组3组Apelin-13、AngⅡ、NO水平比较,差异有统计学意义(F分别为31.125、64.720、21.024,均P<0.001)。AVF狭窄患者中,Apelin-13与NO呈正相关(r=0.447,P<0.001),AngⅡ与NO呈负相关(r=-0.611,P<0.001)。Apelin-13对AVF狭窄的诊断AUC为0.780(95%CI:0.679~0.880),AngⅡ对AVF狭窄的诊断AUC为0.844(95%CI:0.760~0.927),Apelin-13、AngⅡ对AVF狭窄诊断的AUC比较,差异无统计学意义(Z=0.959,P=0.337)。A组、B组和C组的NO、peNOS水平比较,差异有统计学意义(F分别为31.361、11.079,均P<0.001)。结论Apelin-13、AngⅡ与AVF狭窄患者NO水平均具有相关性,Apelin-13可能通过拮抗AngⅡ对eNOS/NO信号通路进行调控,以抑制内皮细胞凋亡,减轻血管内皮细胞损伤,缓解血液透析患者AVF狭窄程度。Objective To study the expression and activity of angiotensin Ⅱ receptor-like 1 endogenous ligand 13(Apelin-13)and angiotensinⅡ(AngⅡ)in autologous arteriovenous fistula(AVF).Methods Ninety patients on hemodialysis were selected and divided into stenosis group(n=45)and normal group(n=45)according to the presence or absence of AVF stenosis.Forty-five patients with chronic kidney disease admitted to the hospital in the same period were selected as the control group.Serum levels of Apelin-13,AngⅡ,and nitric oxide(NO)in the three groups were compared.The correlation between Apelin-13,AngⅡand NO levels was analyzed in stenosis group.ROC curve was used to analyze the diagnostic value of Apelin-13 and AngⅡfor AVF stenosis.Human umbilical vein endothelial cells(HUVECs)were used to analyze the expression of NO,phosphorylated endothelial nitric oxide synthase(peNOS)and endothelial nitric oxide synthase(eNOS)after stimulation with AngⅡ(group A),Apelin-13(group B)and AngⅡcombined with Apelin-13(group C).Results The differences of serum Apelin-13,AngⅡ,and NO levels were statistically significant among stenosis group,normal group and control group(F=31.125,64.720 and 21.024 respectively,P=0.001).In stenosis group,Apelin-13 was positively correlated with NO(r=0.447,P<0.001),and AngⅡwas negatively correlated with NO(r=-0.611,P<0.001).The AUC of Apelin-13 for the diagnosis of AVF stenosis was 0.780(95%CI=0.679~0.880),and the AUC of AngⅡfor the diagnosis of AVF stenosis was 0.844(95%CI=0.760~0.927);no significant difference was found between AUC values of Apelin-13 and AngⅡfor the diagnosis of AVF stenosis(Z=0.959,P=0.337).The differences of NO and peNOS levels were statistically significant among groups A,B and C(F=31.361 and 11.079 respectively,P<0.001).Conclusion Serum Apelin-13 and AngⅡlevels were correlated with NO level in patients with AVF stenosis.Apelin-13 may regulate the eNOS/NO signaling pathway by antagonizing AngⅡto inhibit endothelial cell apoptosis,reduce vascular endothelial cell damage

关 键 词：血管紧张素Ⅱ受体样1受体内源性配体13 血管紧张素Ⅱ 自体动静脉内瘘狭窄 一氧化氮 

分 类 号：R318.16[医药卫生—生物医学工程]