甘草酸对动脉粥样硬化斑块的消退作用

来源 :中国医院药学杂志 | 被引量 : 0次 | 上传用户:jim2y
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目的:探讨甘草酸对高脂血症模型鼠,载脂蛋白E基因敲除(apoE-/-)小鼠,血管壁动脉粥样硬化(As)斑块的消退作用及可能机制。方法:9周龄的雄性apoE-/-小鼠16只,经高脂饮食加重高脂血症,8周后更换为普食,随机分组,甘草酸组采用160 mg·kg-1·d-1的剂量灌胃,对照组给予同等生理盐水灌胃,6周后小鼠安乐死,采取眼球后静脉血测量血浆总胆固醇(TC)、三酰甘油(TG)水平,酶联免疫吸附法(ELISA)检测血中单核细胞趋化因子(MCP-1)的水平,取小鼠胸腹主动脉分析血管内壁As斑块面积,主动脉窦部组织冰冻切片进行油红O染色分析斑块面积;利用原代培养的小鼠腹腔巨噬细胞检测甘草酸对炎症因子及脂代谢相关因子mRNA表达的调控作用。结果:高脂饮食明显加重小鼠血脂紊乱,改为普食后,对照组血脂水平仍高于基础值,而甘草酸组则明显降低了血清TC、TG水平及血MCP-1水平,甘草酸组小鼠主动脉窦As斑块的面积比对照组下降23%,主动脉血管内壁斑块减少约40%,同时细胞实验表明甘草酸能显著降低脂多糖(LPS)刺激下巨噬细胞IL-6的水平,并可诱导细胞膜上ATP结合盒转运体A1(ABCA1)的表达升高。结论:甘草酸可通过改善小鼠血脂水平,降低炎症反应,而表现出较强的消退早期As斑块的作用。 Objective: To investigate the regressive effect of glycyrrhizin on hyperlipidemia model mice, apolipoprotein E gene knockout (apoE - / -) mice and atherosclerotic plaque of blood vessel wall and its possible mechanism. Methods: Totally 16 male apoE - / - mice aged 9 weeks were given hyperlipidemia by hypercholesterolemia. After 8 weeks, they were changed to general diet and randomly divided into groups. The rats in glycyrrhizin group were treated with 160 mg · kg -1 · d- 1 in the control group were given the same physiological saline gavage, 6 weeks after the mice were euthanized, after taking the retro-orbital venous blood plasma total cholesterol (TC), triglyceride (TG) levels, enzyme-linked immunosorbent assay (ELISA ) To detect the level of monocyte chemoattractant (MCP-1) in the blood. The aorta of the thoracoabdominal and abdominal aorta was used to analyze the area of ​​As plaque in the inner wall of the blood vessel and the frozen section of the aortic sinus was used to analyze the plaque area by oil red O staining. Primary cultured mouse peritoneal macrophages were used to detect the regulation of glycyrrhizin on the mRNA expression of inflammatory factors and lipid metabolism. Results: High-fat diet significantly aggravated the dyslipidemia in mice. After the general diet, the levels of serum lipids in the control group were still higher than those in the baseline, while those in the glycyrrhizin group significantly reduced the level of serum TC, TG and serum MCP- Compared with the control group, the area of ​​As plaque in the aortic sinus of the mice decreased by 23% and the plaque in the aorta decreased by about 40%. Meanwhile, the cell experiments showed that glycyrrhizin could significantly reduce the levels of IL- 6 levels and induce an increase in the expression of ATP-binding cassette transporter A1 (ABCA1) on the cell membrane. CONCLUSION: Glycyrrhizic acid can exert strong effect on regression of early As plaque by improving blood lipid level and reducing inflammation in mice.
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