腺病毒介导Profurin表达改善ApoE－/－小鼠斑块稳定性

Adenovirus mediated Profurin expression improved the plaque stability of ApoE－/－ mice

摘要:

目的]探究腺病毒介导Profurin(PF)表达对ApoE－/－小鼠斑块稳定性的影响。 [方法]用高脂饲料喂养ApoE－/－小鼠8周,给予腺病毒(ADV)介导的PF干预,继续高脂饲料喂养4周,分离主动脉根部,进行动脉粥样硬化斑块面积分析和免疫组织化学分析。用荧光供体法检测血浆磷脂转运蛋白(PLTP)活性,用酶学试剂盒检测血浆总胆固醇(TC)、甘油三酯(TG),用快速蛋白液相色谱进行脂蛋白谱分析。 [结果]与对照组相比,ADV-PF组小鼠血浆TC和TG水平、PLTP活性以及循环中肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)水平均显著下降(P＜0.01)；ADV-PF组小鼠全长主动脉内表面动脉粥样硬化病变无明显变化,但主动脉根部斑块面积和斑块内脂质面积均缩小(P＜0.01),巨噬细胞含量显著降低(P＜0.01),平滑肌细胞和胶原面积无明显差别；斑块内基质金属蛋白酶9含量显著降低(P＜0.05)。 [结论]过表达PF能在一定程度上减轻动脉粥样硬化并降低循环炎症因子水平,有效改善ApoE－/－小鼠斑块稳定性。

Abstract:

Aim To investigate the effect of adenovirus (ADV)-mediated Profurin (PF) expression on the plaque stability of ApoE－/－ mice. Methods ApoE－/－ mice were fed with high-fat diet for 8 weeks, and then treated with ADV-mediated PF intervention, followed by high-fat diet for 4 weeks. Aortic roots were isolated for atherosclerotic plaque area analysis and immunohistochemical analysis. Plasma phospholipid transfer protein (PLTP) activity was detected by fluorescence donor essay, plasma total cholesterol (TC) and triglyceride (TG) were measured by enzyme assay kits, and fast protein liquid chromatography was used for lipoprotein profile analysis. Results Compared with the control group, the plasma TC and TG levels, PLTP activity and circulating tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in ADV-PF group were significantly decreased (P＜0.01). In the ADV-PF group, there was no significant change in atherosclerotic lesions on the inner surface of the full-length aorta, but the plaque area and lipid area in the aortic root were reduced (P＜0.01), the content of macrophages was significantly decreased (P＜0.01), and the smooth muscle cells and collagen area were not significantly different. The content of matrix metalloproteinase-9 in plaque was significantly decreased (P＜0.05). Conclusion Overexpression of PF can alleviate atherosclerosis and reduce the levels of circulating inflammatory factors to a certain extent, and effectively improve the plaque stability of ApoE－/－ mice.