Src调控动脉粥样硬化斑块中巨噬细胞脂质累积的机制研究

The underlying mechanism for Src regulating the lipid accumulation within macrophages in atherosclerosis plaques

目的:探究Src对动脉粥样硬化斑块中巨噬细胞脂质累积的调控机制。方法:取发生动脉粥样硬化的股动脉(病变组)与正常乳内动脉(对照组)组织,免疫组织化学法检测组织中磷酸化Src表达水平。采用Src干扰小RNA(siRNA)转染和Src蛋白激酶特异性抑制剂PP2处理巨噬细胞,通过油红O染色及比色法测定其胞内脂质含量,探究Src对巨噬细胞脂质累积的作用机制。通过构建C57BL/6小鼠动脉粥样硬化模型,进一步确定Src在动脉粥样硬化过程中的重要作用。结果:与正常对照相比较,动脉粥样硬化斑块中磷酸化Src表达量明显升高(P<0.05),且与CD68阳性细胞(巨噬细胞)共定位良好;降低Src表达水平和活性后,氧化低密度脂蛋白(oxLDL)诱导的巨噬细胞内脂质累积减少(P<0.05)。结论:Src可能通过介导巨噬细胞脂质累积调控动脉粥样硬化斑块的形成。

Objective To study the underlying mechanism for Src regulating the lipid accumulation within macrophages in atherosclerosis plaques. Methods Human femoral arteries with atherosclerotic plaques and human normal internal thoracic arteries （as control） were collected for detecting the expression of phosphorylated Src （p-Src）. Inhibited the function of Src within macrophages via transfecting Src small interfering RNA （siRNA）（lowering the total expression of Src） into the cells or treating the cells with PP2 （specific inhibitor of Src） and compared the contents of intracellular lipid and cholesterol by oil red O staining and colorimetric analysis for investigating the mechanism of Src in regulating the lipid accumulation within macrophages. Then atherosclerosis model in the C57BL/6 mice was established for further confirming the role of Src during the process of atherosclerosis. Results P-Src was highly expressed within macrophages of atberoscle- rosis plaques （P〈0.05）. The inhibition of Src could lower the contents of both lipid and cholesterol induced by oxygenized low density lipoprotein （oxLDL） （P〈0.05）. Conclusions The role of Src in the development of atherosclerosis might be via mediating the lipid accumulation in macrophages.