血浆氧化低密度脂蛋白自身抗体与小鼠动脉粥样硬化的相关性研究

Preliminary Study on Correlation between Plasma Titers of Ox-LDL Auto-antibody and Extent of Atherosclerosis in Mice

目的探索可预测小鼠动脉粥样硬化程度的血浆指标。方法C57BL／6J小鼠给予普通饮食喂养12周。载脂蛋白E基因缺陷小鼠（背景品系为C57BL／6J）分为四组，A组给予高胆固醇饮食（1％胆固醇），B组给予高胆固醇饮食＋罗苏伐他汀（1mg／kg／d）干预，C组给予高胆固醇饮食＋坎地沙坦（1mg／kg／d）干预，D组给予高胆固醇饮食＋罗苏伐他汀（1mg／kg／d）＋坎地沙坦（1mg／kg／d）干预。12周后测定血浆中氧化低密度脂蛋白自身抗体的滴度与动脉粥样硬化发展的程度。结果C57BL／6J小鼠无动脉粥样硬化，而A组小鼠出现广泛动脉粥样硬化。B组和C组小鼠动脉粥样硬化的程度降低，而D组小鼠动脉粥样硬化的程度更低。A组小鼠血浆中四种抗体，包括铜低密度脂蛋白IgG，铜低密度脂蛋白IgM，丙二醛化低密度脂蛋白IgG和丙二醛化低密度脂蛋白IgM的水平均高于C57BL／6J小鼠（P〈0．01）。与A组小鼠相比，B、C和D组小鼠血浆中仅铜低密度脂蛋白IgG的滴度降低，且降低程度与动脉粥样硬化降低程度一致。与C57BL／6J小鼠相比，A组小鼠血浆中氧化低密度脂蛋白水平显著降低（P〈0．01）。B组和C组小鼠氧化低密度脂蛋白的血浆水平与A组无显著差异，仍明显低于C57BL／6J小鼠，但D组小鼠血浆氧化低密度脂蛋白水平恢复正常。结论铜低密度脂蛋白IgG的血浆水平与动脉粥样硬化的进展及消退呈高度正相关，或可作为动脉粥样硬化程度的预测指标。

Objective＇ To identify a potential plasma marker for the prediction of atherosclerosis in mice. Methods C57BL/6J mice were fed on regular diet. Apo-E deficient mice （on C57BL/6J background） were divided into four groups, group A： high cholesterol diet （1% cholesterol） alone, group B： highcholesterol diet with rosuvastatin （1mg/kg/d）, group C： high-cholesterol diet with candesartan （1 mg/kg/d）, and group D： high-cholesterol diet with rosuvastatin and candesartan. All the mice groups were fed for 12 weeks. Plasma titers of ox-LDL auto-antibodies in relation to the extent of atherosclerosis in these mice were measured. Results C57BL/6J mice had no atherosclerosis, whereas mice in group A had extensive atherosclerosis. The extent of atherosclerosis was decreased in group B and C mice, despite high-cholesterol diet. Moreover, the extent of atherosclerosis was further decreased in group D mice. The plasma titers of four ox-LDL auto-antibodies were measured. It was found that the mean values of all antibodies, includ- ing Cu-LDL-IgG, Cu-LDL-IgM, MDA-LDL-IgG and MDA-LDL-IgM, were higher in group A mice than in C57BL/6J mice （P〈0.01）. Compared with group A mice, group B,C and D mice had lower plasma titers of Cu-LDL-IgG, which was consistent with the decrease in extent of atherosclerosis. Compared with that of C57BL/6J mice, plasma level of ox-LDL reduced in group A mice （P〈0.01）. Although plasma level of ox-LDL also reduced in group B and C mice, it was restored back to normal level in group D mice. Conclusion The plasma titer of Cu-LDL-IgG is consistent with the progression and regression of atherosclerosis and it may serve as a marker for the prediction of atherosclerosis.