血管紧张素(1-7)对CD40及CD40配体信号通路及活化黏附分子的抑制作用

摘要

目的 观察血管紧张素1-7[Ang-(1-7)]对血管紧张素Ⅱ(AngⅡ)诱导的人脐静脉内皮细胞中细胞间黏附分子1(ICAM-1)和血管细胞黏附分子1(VCAM 1)表达的影响及作用机制是否与CD40及CD40配体(CD40L)通路有关.方法 人脐静脉内皮细胞培养后,分6组:对照组;AngⅡ组;低、中和高剂量组[Ang(1-7)10、100和1000nmol/L预处理];阻断剂组(A-779预处理).用RT-PCR法检测ICAM-1、VCAM-1和CD40、CD40L mRNA表达.结果 与对照组比较,AngⅡ组ICAM-1、VCAM-1和CD40、CD40L mRNA表达显著升高(P＜0.05);与AngⅡ组比较,低、中和高剂量组ICAM-1、VCAM-1和CD40、CD40LmRNA的表达逐渐下降(P＜0.05),其中ICAM-1、VCAM-1 mRNA表达分别下降25％、58％、69％和30％、53％、62％;CD40、CD40L mRNA表达分别下降35％、48％、61％和26％、54％、68％;阻断剂组与AngⅡ组上述指标比较无显著差异(P＞0.05).结论 Ang-(1-7)可以抑制炎症通路CD40/CD40L活化,进而下调黏附分子ICAM-1、VCAM-1的表达;Ang-(1-7)的抗炎机制是首先与Mas受体结合,进而发挥抑制CD40/CD40L通路的作用.%Objective To study the inhibitory effect of Ang 1-7 on expression of Ang Ⅱ-induced intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in cultured human umbilical vein endothelial cells (HUVEC) and whether its mechanism is related with the CD40/CD40L pathway.Methods Cultured HUVEC were divided into control group,Ang Ⅱ group,low AngⅡ dose (10 nmol/L) group,medium AngⅡ dose (100 nmol/L) group,high AngⅡ dose (1000 nmol/L) group and blocker (A-779) group.Expressions of ICAM-1,VCAM-1,CD40/CD40L mRNA were detected by RT-PCR.Results The expression levels of ICAM-1,VCAM-1,CD40/CD40L mRNA were significantly higher in Ang Ⅱ group than in control group (P＜0.05)and were significantly lower in low AngⅡ dose group,medium Ang Ⅱ dose group and high Ang Ⅱ dose group than in Ang Ⅱ group (P＜0.05).The expression of ICAM-1 and VCAM-1 decreased by 25％,58％,69％ and 30％,53％,62％,and that of CD40/CD40L mRNA decreased by 35％,48％,61％ and 26 ％,54％,68％.No significant difference was found in the expressions of ICAM-1,VCAM 1,CD40/CD40L mRNA between Ang Ⅱ group and blocker group (P＞0.05).Conclusion Ang 1-7 can inhibit the activation of CD40/CD40L pathway and downregulate the expression of ICAM-1 and VCAM-1 in HUVEC by binding to their specific receptor Mas.