【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。

【Abstract】Objective To study the expression and activity of angiotensin II receptor-like 1 endogenous ligand 13 (Apelin-13) and angiotensin Ⅱ (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, AngⅡ and NO levels was analyzed in stenosis group. ROC curve was used to analyze the diagnostic value of Apelin-13 and AngⅡ for 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 AngⅡ combined with Apelin-13 (group C). Results The differences of serum Apelin-13, AngⅡ, and NO levels were statistically significant among steno-sis 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 AngⅡ was 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 AngⅡ for 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 AngⅡ for 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 Ang Ⅱ levels were correlated with NO level in patients with AVF stenosis. Apelin-13 may regulate the eNOS/NO signaling
pathway by antagonizing Ang Ⅱ to inhibit endothelial cell apoptosis, reduce vascular endothelial cell damage and relieve the degree of AVF stenosis in hemodialysis patients.