西洋参茎叶总皂苷对载脂蛋白E基因敲除小鼠血脂及脂质代谢相关基因周脂素和CD36表达的影响

The Effect of Panax Quinquefolius Saponin on the Gene Expressions of Perilipin and CD36 Assosciated with Lipid Metabolism of Apolipoprotein E-Gene Knockout Mice

目的观察西洋参茎叶总皂苷对载脂蛋白E基因敲除小鼠斑块成分及脂质代谢相关基因周脂素和清道夫受体CD36表达的影响,探讨西洋参茎叶总皂苷稳定动脉粥样硬化斑块的作用及可能机制。方法33只6-8周龄小鼠载脂蛋白E基因敲除小鼠予高脂饮食喂养13周后,待其形成成熟的动脉粥样硬化斑块后,随机分为3组：模型组、西洋参茎叶总皂苷组、辛伐他汀组（阳性对照组）,每组11只。继续高脂喂养,并按体重比折算给予小鼠临床推荐剂量的相应药物治疗13周,处死动物,检测血脂,取心脏和主动脉,每只小鼠均取主动脉根部的4个切面,分别行HE染色和Movat染色,观察并计算各组小鼠主动脉粥样斑块内脂质核心大小,脂质成分与胶原成分比值。实时荧光定量PCR法检测主动脉内周脂素和CD36 mRNA的表达。结果给药13周后,与模型组比较西洋参茎叶总皂苷组小鼠主动脉斑块内脂质核心面积以及脂质成分与胶原成分比值明显减小（P〈0.01）,血清高密度脂蛋白显著升高（P〈0.01）。而主动脉内周脂素和CD36 mRNA的表达与模型组比较均显著降低（P〈0.05）。结论在临床推荐剂量上,西洋参茎叶总皂苷可通过改善载脂蛋白E基因敲除小鼠主动脉斑块内部成分,尤其是减少斑块内脂质含量来起到稳定动脉硬化斑块的作用,其机制可能与抑制脂质代谢相关基因周脂素和清道夫受体CD36 mRNA的表达有关。

Aim To observe the effects of panax quinquefolius saponin on plaque content and the gene expressions of perilipin and scavenger receptor CD36 assosciated with lipid metabolism of ApoE-gene knockout mice and explore the effect of panax quinquefolius saponin on atherosclerotic plaque stability and its possible mechanism.Methods Thirty-three ApoE knockout mice had been fed with a high-fat diet for 13 weeks until the mature atherosclerotic plaques formed.Thereafter, they were randomized to three groups： control group,panax quinquefolius saponin group,simvastatin group（positive control group）.Two drug-treated groups were treated with respective drug in clinical recommended doses for another 13 weeks accompancied by feeding high-fat diet.Then all the mice were sacrificed at the end of experiment,their blood was collected for determining the concentrations of blood lipids.The morphology and composition of atherosclerotic plaques in aortic roots were examined in tissue sections.Four sections were choosed and stained with Movat and HE stains respectively.The lipid core in plaque as well as the ratio of lipid to collagen content in plaque in each mouse were measured and counted.The gene expressions of perilipin and CD36 were determined by Real-time fluorescent quantitative PCR technology.Results After treated drugs for 13 weeks,panax quinquefolius saponin group significantly reduced the lipid core as well as the ratio of lipid to collagen content in and the concentration of HDL in serum was significantly increased（P〈 0.01）.The gene expression of perilipin and CD36 in aorta were significantly downregulated compared with controls （P〈0.05, P〈0.01）. Conclusions In a clinical recommended dose, panaxquinquefolius saponin may stabilize atheroselexofic plaque in aorta of ApoE-gene knockout mice by improving plaque contents, especially lipid content in plaque, whose mechanism may be related to the inhibition on the gene exressions of perilipin and scavenger receptor CD36 assosciated with lipid metabolism.