血管紧张素(1-7)对血管紧张素Ⅱ诱导的人脐静脉内皮细胞血凝素样氧化型低密度脂蛋白受体1表达的影响
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Effects of Angiotensin(1-7) on the Expression of Lectin-Like Oxidized Low Density Lipoprotein Receptor-1 in Human Umbilical Vein Endothelial Cells Induced by Angiotensin Ⅱ
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    摘要:

    目的观察血管紧张素(1-7)对血管紧张素Ⅱ诱导的人脐静脉内皮细胞血凝素样氧化型低密度脂蛋白受体1表达水平的影响并探讨其可能作用机制。方法采用胰蛋白酶消化法原代培养人脐静脉内皮细胞,取2~5代用于实验,培养的人脐静脉内皮细胞随机分为对照组、血管紧张素Ⅱ组、血管紧张素(1-7)组、血管紧张素Ⅱ+血管紧张素(1-7)组、血管紧张素Ⅱ+血管紧张素(1-7)+血管紧张素(1-7)特异性受体拮抗剂A-779组,通过半定量逆转录聚合酶链反应和流式细胞术分别检测血凝素样氧化型低密度脂蛋白受体1基因和蛋白表达水平;用免疫印迹法检测p38丝裂原活化蛋白激酶磷酸化的表达水平。结果血管紧张素Ⅱ(10~(-6) mol/L)可以诱导血凝素样氧化型低密度脂蛋白受体1表达增加(P<0.05),血管紧张素(1-7)(10~(-9)~10~(-6) mol/L)随着浓度的增加抑制血管紧张素Ⅱ诱导的血凝素样氧化型低密度脂蛋白受体1表达水平增强(P<0.05);血管紧张素(1-7)特异性受体拮抗剂A-779可阻断血管紧张素(1-7)的上述效应(P<0.05)。与对照组相比,血管紧张素Ⅱ(10~(-6) mol/L)诱导后p38丝裂原活化蛋白激酶磷酸化表达水平显著增加(P<0.05);血管紧张素(1-7)(10~(-9)~10~(-6) mol/L)随着浓度的增加抑制血管紧张素Ⅱ诱导的p38丝裂原活化蛋白激酶磷酸化表达水平增强(P<0.05),血管紧张素(1-7)特异性受体拮抗剂A-779可阻断血管紧张素(1-7)的上述效应(P<0.05)。结论血管紧张素Ⅱ可诱导血凝素样氧化型低密度脂蛋白受体1及p38丝裂原活化蛋白激酶磷酸化表达增加,血管紧张素(1-7)抑制血管紧张素Ⅱ的上述效应,并且是通过其特异性受体发挥作用。

    Abstract:

    Aim To investigate the effects of Angiotensin(1-7)(Ang(1-7)) on the expression of lectin-like oxidized low density lipoprotein receptor-1(LOX-1) in human umbilical vein endothelial cells(HUVEC) induced by angiotensinⅡ(AngⅡ).Methods HUVEC were isolated and cultured.Cultured HUVEC were incubated for 24 h with Ang-(1-7),AngⅡ,Ang(1-7)+A-779,Ang(1-7)+AngⅡ,A-779+AngⅡ+Ang(1-7),respectively.And cultured HUVEC without incubating stimulator were chosen as controls.The expression of the mRNA and protein of LOX- 1 was measured by RT-PCR and flow cytometry methods respectively.The expression of the phosphorylation of p38 mitogen activated protein kinase(MAPK) was determined by Western blotting.Results Compared with the AngⅡgroup, Ang(1-7) dose-dependently inhibited the expression of LOX-1 in HUVEC(P<0.05).Compared with control group, the expression of the phosphorylation of p38 MAPK increased significantly in AngⅡgroup(P<0.05),while it was a little in Ang(1-7) group and A-779 group(P>0.05).The expression of the phosphorylation of p38 MAPK reduced in AngⅡ+Ang(1-7)group compared with AngⅡgroup(P<0.01).The expression of the phosphorylation of p38 MAPK had no significant change in AngⅡ+Ang(1-7)+A-779 group(P>0.05).Conclusion Ang(1-7) concentration dependently attenuate the expression of LOX-1 induced by AngⅡin HUVEC through its specfic receptor MAS,Ang(1-7) could inhibit the expression of the phosphorylation of p38 MAPK induced by AngⅡin HUVEC,and then inhibit the AngⅡ-induced LOX-1 espression.

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杨慧宇,杨志明,边云飞,张娜娜,梁斌,肖传实.血管紧张素(1-7)对血管紧张素Ⅱ诱导的人脐静脉内皮细胞血凝素样氧化型低密度脂蛋白受体1表达的影响[J].中国动脉硬化杂志,2009,17(6):465~469.

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  • 收稿日期:2009-02-20
  • 最后修改日期:2009-04-02
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