血管紧张素-(1-7)对血管紧张素Ⅱ诱导的脐静脉内皮细胞MCP-1和ICAM-1表达的影响

Influence of angiotensin-(1-7) on the secretion of MCP-1 and ICAM-1 in cultured human umbilical vein cells induced by angiotensin Ⅱ

目的:研究血管紧张素-(1-7)[Ang-(1-7)]对血管紧张素Ⅱ(AngⅡ)诱导的脐静脉内皮细胞(HUVEC)单核细胞趋化蛋白-1(MCP-1)和细胞间黏附分子-1(ICAM-1)的影响,阐明Ang-(1-7)对AngⅡ在炎症方面的拮抗作用。方法:体外培养HUVEC,随机分为:对照组;AngⅡ组;Ang-(1-7)组;AngⅡ+Ang-(1-7)组;AngⅡ+Ang-(1-7)+Ang-(1-7)受体阻断剂A-779组。以ELISA法和半定量RT-PCR法从蛋白和mRNA水平检测MCP-1和ICAM-1的表达情况。结果:与对照组比,AngⅡ(100nmol/L)使MCP-1和ICAM-1的蛋白和mRNA表达明显增加(P<0.05);Ang-(1-7)(1000nmol/L)使MCP-1和ICAM-1的蛋白和mRNA表达降低(P<0.05);混合刺激组中,与AngⅡ组比较,Ang-(1-7)(10nmol/L、100nmol/L、1000nmol/L、10000nmol/L)呈剂量依赖性地抑制AngⅡ诱导的HUVECMCP-1、ICAM-1蛋白和mRNA的表达(P<0.05),Ang-(1-7)浓度为1000nmol/L时,虽然蛋白和mRNA表达仍高于对照组,但无显著差异(P>0.05);加入A-779组与AngⅡ组比较无显著差异(P>0.05)。结论:Ang-(1-7)通过其特异性受体MAS拮抗AngⅡ诱导的HUVECMCP-1和ICAM-1的表达,并呈浓度依赖性。

AIM ： To explore the influence of angiotensin - （ 1 - 7） [ Ang - （ 1 - 7） ] on the secretion of mono- cyte chemoattractant protein （ MCP - 1 ） and intercellular adhesion molecule - 1 （ ICAM - 1 ） in human umbilical vein endothelial cells （HUVEC） induced by angiotensin Ⅱ （ Ang Ⅱ ）, and to clarify the prevent effect of Ang - （ 1 - 7） on the inflammation induced by Ang Ⅱ. METHODS： The cultured HUVEC were randomly divided into control group, Ang Ⅱ group, Ang-（1-7） group, Ang-（1-7） ＋ AngⅡ group, andA-779 ＋ Ang-（1-7） ＋ AngⅡ group. The expressions of MCP - 1 and ICAM - 1 in protein level and mRNA level were detected by enzyme linked immunosorbent assay （ELISA） and reverse transcription polymerase chain reaction （RT- PCR）. RESULTS： Compared with the control group, 100 nmol/L Ang Ⅱ distinctly increased the protein and mRNA expression of MCP - 1 and ICAM - 1 in HUVEC （ P 〈 0. 05）. Ang - （ 1 - 7 ） （ 1 000 nmol/L） decreased the protein and mRNA expression of MCP - 1 and ICAM - 1 （ P 〈 0. 05）. Compared with the Ang Ⅱ group, Ang - （ 1 - 7） inhibited the protein and mRNA expressions of MCP - 1 and ICAM - 1 in HUVEC induced by Ang 1I in a dose - dependent manner （ P 〈 0. 05 ）. When the concentration of Ang - （ 1 - 7 ） was up to 1 000 nmol/L, the expressions of ICAM - 1 and VCAM - 1 were more than that in control group, but was not statistically significant （ P 〉 0. 05 ）. No significant difference between the A - 779 group and Ang Ⅱ group was observed （ P 〉 0. 05）. CONCLUSION ： Ang - （ 1 - 7） inhibits the secretion of MCP - 1 and ICAM - 1 in cultured HUVEC in a concentration dependent matter induced by Ang Ⅱ. The inhibitory effect of Ang - （ 1 - 7 ） may be through its specific receptor.