甘草酸对动脉粥样硬化斑块的消退作用

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。

Regressive effects of glycyrrhizic acid on atherosclerosis plague

OBJECTIVE To investigate the regressive effect and its mechanism of glycyrrhizic acid on hypercholesterolemia model, apolipoprotein E gene knockout (apoE^-/-) mice. METHODS Sixteen male apoE^-/- mice fed with Western diet for 8 weeks, then changed to chow diet with glycyrrhizic acid (160 mg·kg^-1·d^-1 ) or saline intragastrically for 6 weeks. Then the mice were euthanized, the levels of plasma total cholesterol (TC), triglyceride (TG) were determined, and monocyte chemotactic factor 1 (MCP-1) was detected by enzyme linked immunosorbent assay. The extent of atherosclerosis plague was examined by oil red O-stained analysis both in cross-sections of the aortic root and aorta en face analysis.The regulation function of glycyrrhizic acid on mRNA expression of inflammatory factor and lipid metabolism related protein were detected by real-time RT-PCR using cultured peritoneal macrophage. RESULTS Hyperlipidemia of apoE^-/- mice was aggravated when animals were fed with Western diet. After chow diet, the serum lipid levels of control group were still higher than the basic levels, but glycyrrhizic acid could reduce the serum levels of TC, TG and MCP-1. Furthermore, in glycyrrhizic acid group, atherosclerotic plaque area of aortic root was reduced by 23% proximately versus control mice, and atherosclerotic plague of aorta was lowered by nearly 40%. In cultured macrophages, glycyrrhizic acid could protect cells against LPS-induced inflammation by suppressing interleukin 6 (IL-6) mRNA level and upregulating ABCA1 expression. CONCLUSION Glycyrrhizic acid improves the plasma lipid profile of atherosclerotic mice, reduces inflammation, and regresses the early stage atherosclerotic plaque.