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目的 :研究低密度脂蛋白对小鼠腹腔巨噬细胞胰岛素样生长因子 - 1受体 (IGF - 1R)、磷酸化细胞外信号调节激酶 (p -ERK)、Bcl- 2和Bax表达的影响 ,从而探讨低密度脂蛋白诱导巨噬细胞存活的机理。方法 :应用免疫细胞化学和Westernblotting方法 ,检测低密度脂蛋白对小鼠腹腔巨噬细胞IGF - 1R、p -ERK、Bcl- 2和Bax表达的影响。结果 :氧化型低密度脂蛋白 (oxLDL)以剂量和时间依赖的方式增加IGF - 1R的表达。oxLDL刺激 5min后 ,p -ERK表达最高。oxLDL诱导ERK从细胞浆内转至胞核内。给予IGF - 1R抗体后 ,oxLDL诱导p -ERK表达降低 ,并且ERK转核过程消失。oxLDL以浓度和时间依赖的方式增加Bcl- 2的表达 ,降低Bax的表达。给予ERK抑制剂PD980 5 9后 ,oxLDL诱导Bcl- 2表达降低 ,而Bax蛋白表达明显增高。自然型LDL对这 4种蛋白的表达无明显影响。结论 :oxLDL诱导巨噬细胞存活至少是通过增加IGF - 1R的表达及ERK磷酸化实现的 ,并且可能存在其他的途径参与oxLDL诱导巨噬细胞存活。
Objective: To study the effect of low density lipoprotein on the expression of insulin - like growth factor - 1 receptor (IGF - 1R), phosphorylated extracellular signal - regulated kinase (p - ERK), Bcl - 2 and Bax in murine peritoneal macrophages, To investigate the mechanism of low density lipoprotein-induced macrophage survival. Methods: Immunocytochemistry and Western blotting were used to detect the effect of LDL on the expression of IGF - 1R, p - ERK, Bcl - 2 and Bax in mouse peritoneal macrophages. Results Oxidized low density lipoprotein (oxLDL) increased IGF - 1R expression in a dose - and time - dependent manner. After 5min oxLDL stimulation, p -ERK expression was the highest. OxLDL induces the transfer of ERK from the cytoplasm to the nucleus. After administration of IGF - 1R antibody, oxLDL induced a decrease of p - ERK expression and the process of ERK translocation disappeared. OxLDL increased Bcl-2 expression in a concentration- and time-dependent manner and decreased Bax expression. After administration of PD98059, a ERK inhibitor, oxLDL induced a decrease in Bcl-2 expression and a significant increase in Bax protein expression. Natural LDL had no significant effect on the expression of these four proteins. CONCLUSION: OxLDL - induced macrophage survival is at least augmented by increased IGF - 1R expression and ERK phosphorylation, and there may be other pathways involved in oxLDL - induced macrophage survival.