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目的研究3种不同联合用药方案对大鼠动脉粥样硬化斑块稳定及高密度脂蛋白功能的影响。方法将动脉粥样硬化模型SD大鼠随机分为5组,对照组、高脂组、依折麦布联合辛伐他汀(依/辛)组、依折麦布、辛伐他汀联合普罗布考(依/辛/普)组、依折麦布、阿托伐他汀联合普罗布考(依/阿/普)组。对照组、高脂组给予等体积生理氯化钠溶液灌胃,其余3组分别给予药物灌胃,均为8周。称量体质量、不同部位脂肪、检测血清生化指标及病理变化,综合评价不同联合用药治疗方案对动脉粥样硬化斑块稳定及高密度脂蛋白功能的影响。结果给大鼠灌胃8周后,体质量、体质量差值变化以依/辛/普组变化较为明显;脂肪质量绝对值、相对值变化以依/阿/普组较为明显;血清生化指标变化,总胆固醇、甘油酸酯、高密度脂蛋白均有不同程度改善。其中高密度脂蛋白指标以依/阿/普组改善最为明显;血清胰岛素水平变化,联合用药治疗后依/辛组、依/阿/普胰岛素、胰岛素抵抗分别较高脂组明显升高,以依/阿/普组较为明显;高密度脂蛋白功能指标对氧磷酶1(PON1)以依/阿/普组变化最为明显;病理各项指标显示,联合用药治疗后依/阿/普组、依/辛/普组斑块改善明显优于依/辛组。结论依/辛组、依/辛/普组、依/阿/普组均有改善大鼠动脉粥样硬化的作用,其中以依/阿/普组较为明显。PON1浓度变化表明普罗布考虽降低高密度脂蛋白浓度,但可能在提高高密度脂蛋白功能中发挥了重要作用,其可能成为临床降脂、稳定斑块治疗的新选择。
Objective To study the effects of three different combination regimens on the stability of atherosclerotic plaque and the function of high density lipoprotein in rats. Methods Atherosclerotic SD rats were randomly divided into 5 groups: control group, hyperlipidemia group, ezetimibe combined with simvastatin (E / Xin) group, ezetimibe, simvastatin combined with probucol (By / Xin / Pu) group, ezetimibe, atorvastatin combined with probucol (according / A / P) group. Control group, high-fat group were given equal volume of physiological sodium chloride solution, the other three groups were given drug gavage, were 8 weeks. Weigh body mass, fat in different parts of the serum biochemical markers and pathological changes, a comprehensive evaluation of different combinations of drugs on the treatment of atherosclerotic plaque stability and high-density lipoprotein function. Results After 8 weeks of intragastric administration, the change of body weight and body weight difference was more obvious in Yi / Xin / Pu group; the change of absolute value and relative value of fat mass was more obvious in Yi / A / Pu group; Serum biochemical index Changes, total cholesterol, glycerate, high-density lipoprotein were improved to varying degrees. Among them, the indicators of high density lipoprotein were improved most obviously in group I / A / P; the change of serum insulin level was significantly higher in group E / Xin, I / A / P insulin and insulin resistance than that in high-fat group According to / A / Pu group is more obvious; high-density lipoprotein function indicators of paraoxonase 1 (PON1) in accordance with / A / Pu group changes the most obvious; pathological indicators show that after the combination therapy with / A / , According to / Xin / Pu group plaque improvement significantly better than the group according to / Xin. Conclusion The effect of atherosclerosis in rats is improved obviously in Yi / Xin group, Yi / Xin / Pu group and Yi / A / Pu group, especially in Yi / A / Pu group. The change of PON1 concentration shows that probucol may play an important role in improving the function of HDL, though it may decrease HDL concentration, which may become a new choice for clinical treatment of lipid-lowering and stable plaque.