三种联合用药方案对大鼠动脉粥样硬化斑块的影响

Effect of Three Different Regimens on Plaque Stability of Atherosclerosis and Function of High Density Lipoprotein

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 effect of three different combination regimens on plaque stability and HDL function in atherosclerotic rats.Methods SD rats were randomly divided into five groups：control group,high fat group,ezetimibe combined with simvastatin group（ES group）,ezetimibe,simvastatin combined with probucol group（ESP group）and ezetimibe,atorvastatin combined with probucol group（EAP group）.The last three groups were given related drugs for eight weeks by intragastric administration.While the control group and high fat group received an equal volume of saline for eight weeks by intragastric administration.Finally the atherosclerotic plaque and HDL function of treatment groups were evaluated in terms of the changes of body weight,serum parameters,adipose weights and pathological specimens.Results Changes of related indexes were detected after eight weeks of gastric lavage treatment.Body weight and weight gain were more obvious in ESP group.The changes in the absolute value and relative value of fat weight in different organs was more significant in EAP group.The biochemical indicators of serum lipid,including TC,TG and HDL,were improved to different extents.The serum lipid indicator of HDL improved most obviously.The serum indicator of insulin and insulin resistance were significantly increased in ES group,ESP group and EAP group compared with high fat group after eight weeks.Conclusion The symptoms of atherosclerosis in rats were improved in EAP group,ESP group and ES group,especially in EAP group and ESP group.The change of the concentration of oxygen and phosphorus enzyme shows that probucol may play an important role in improving the function of HDL though it can reduce concentrations of HDL.Probucol may become a new choice for clinical treatment of blood lipid and for stabilization of plaques.