胰岛素样生长因子-1受体与磷酸化调节激酶对血管紧张素Ⅱ致动脉粥样硬化作用的影响  

The effects of insulin-like growth factor-1 receptor and phosphorylated extracellular signal-regulated kinase on atheroslerosis induced by AngⅡ

作　　者：马金宝[1] 管思明[2] 

机构地区：[1]北京同仁医院老年病科,北京100730 [2]华中科技大学附属协和医院老年病科

出　　处：《临床心血管病杂志》2004年第12期748-751,共4页Journal of Clinical Cardiology

摘　　要：目的 :研究血管紧张素Ⅱ (AngⅡ )对小鼠腹腔巨噬细胞 (MPM )胰岛素样生长因子 1受体 (IGF 1R)、磷酸化的细胞外信号调节激酶 (p ERK)、Bcl 2和Bax蛋白表达水平的影响 ,探讨AngⅡ影响MPM存活的机制。方法 :利用免疫细胞化学的方法 ,检测IGF 1R、p ERK、Bcl 2和Bax蛋白的表达。 结果 :AngⅡ可明显增加IGF 1R的表达 ,呈浓度和时间依赖性 (P <0 .0 1)。AngⅡ可明显增加 p EKR(P <0 .0 1) ,呈浓度依赖性 ;刺激5min时 ,p ERK表达最高。预先给予α IR 3或PD980 5 9,p ERK的表达明显降低 ,呈浓度依赖性 (P <0 .0 1)。AngⅡ可刺激ERK转核 ,给予α IR 3或PD980 5 9后 ,转核现象消失。AngⅡ明显增加Bcl 2的表达 (P <0 .0 1) ,而降低Bax的表达 (P <0 .0 1) ,呈浓度和时间依赖性 ;预先给予α IR 3或PD980 5 9,Bcl 2的表达明显降低 (P <0 .0 1) ,Bax表达明显增高 (P <0 .0 1) ,呈浓度依赖性。结论 :AngⅡ增加MPMIGF 1R蛋白的表达 ,后者激动下游介导子ERK ,ERK磷酸化增加凋亡抑制基因Bcl 2蛋白的表达 ,降低促凋亡基因Bax蛋白的表达 ,从而促进MPM存活 。Objective: To study the effects of AngⅡon insulin-like growth factor-1 receptor (IGF-1R), phosphorylated extracellular signal-regulated kinase (p-ERK), Bcl-2 and Bax protein expression in mouse peritoneal macrophages (MPM) and investigate the mechanism of AngⅡ-induced macrophage survival. Method:The expression of IGF-1R, p-ERK, Bcl-2 and Bax protein were detected in MPMs cultured with AngⅡ, by using immunocytochemistry method. Result:AngⅡ significantly increased IGF-1R protein expression in a dose and time-dependent manner. AngⅡ could inuduce phosphorylation of ERK in a dose-dependent manner,and P-ERK protein expression peaked at 5 min. Moreover, AngⅡ could induce ERK translocation from cytoplasm to nuclear. When given α-IR-3 or PD98059 p-ERK protein expression was significantly inhibited, and ERK translocation disappeared. AngⅡ increased Bcl-2 protein expression and reduced Bax expression dose and time-dependently. Conclusion:AngⅡ may enhance MPMs IGF-1R protein expression and induce ERK phosphorylation, resulting in Bcl-2 protein expression increase and Bax protein expression decrease. AngⅡ may promote cultured MPMs survival at least by enhancing IGF-1R expression and ERK phosphorylation, and there may be many pathways involved in MPMs survival induced by AngⅡ.

关 键 词：动脉硬化 血管紧张素Ⅱ 巨噬细胞 胰岛素样生长因子-1受体 细胞外信号调节激酶 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]