活血、益气、化痰中药对ApoE基因敲除小鼠主动脉粥样硬化斑块炎症反应的影响

目的探讨活血、益气、化痰中药对ApoE基因敲除小鼠主动脉粥样硬化（AS）斑块成分和炎症反应的影响及其稳定AS斑块作用可能机制。方法70只6～8周龄小鼠ApoE基因敲除小鼠予高脂饮食喂养13周后,待其形成成熟的AS斑块后,随机分为活血组（予丹参酮）、益气组（予西洋参茎叶总皂苷）、化痰组（予瓜蒌提取物）、模型组、阳性对照组（予辛伐他汀）、正常组,相应处理13周后,处死取主动脉根部染色、测量并计算脂质核心占斑块总面积的百分比以及斑块内脂质成分与胶原成分的比值,免疫组织化学染色法观察小鼠主动脉根部粒细胞/巨噬细胞集落刺激因子（GM-CSF）和肿瘤坏死因子α（TNF-α）的蛋白表达,实时荧光定量PCR法检测主动脉内核转录因子κB（NF-κB）mRNA的表达。结果在斑块内脂质核心面积、斑块内脂质成分与胶原成分比值方面,益气、化痰组较模型组均有不同程度的降低;活血组斑块内脂质成分与胶原成分比值明显降低,而斑块内脂核面积与模型组相近。与模型组相比,益气、活血、化痰组小鼠主动脉根部斑块内GM-CSF表达明显减少,对小鼠主动脉斑块内TNF-α表达无明显影响。活血组小鼠主动脉斑块内NF-κBmRNA的表达较模型组降低。结论活血、益气、化痰中药可通过改善斑块内部成分以稳定易损斑块,其机制可能与抑制炎症反应有关。

Effects of Herbs with the Effect of Activating Blood Circulation or Nourishing Qi or Elimating Phlegm on Inflammatory Reaction in Atherosclerotic Plaque in Aorta of ApoE-gene Knockout Mice

Objective： To observe the effects of different TCM therapies on atheroscleotic plaque content and inftammatory reaction in the aortic roots of fat - fed ApoE knockout mice based on the incisivus point of the herbal effective component and explore their effect on atherosclerotie plaque stability and their possible mechanism. Methods： Seventy ApoE knockout mice were fed a high -fat diet for 13 weeks until the mature atherosclerotic plaques formed. Thereafter, they were randomly divided into six groups： activating blood circulation group（treated with tanshinone）, nourishing qi group（treated with panaxquinquefoliumsaponin）, elimating phlegm group（treated with snakegourd fruit extract）, model groups, positive control group（treated with withsimvastatin）, normal control group. Therelater, six groups were treated with respective drug in clinical recommended doses for another 13 weeks accompancied by feeding high- fat diet. The morphology and composition of atherosclerotic plaques in aortic roots were examined in tissue sections. Four seetions were choosed and stained with Movat and HE stains respectively, and the lipid core in plaque as well as the ratio of lipid to collagen content in plaque in each mouse were measured and courted. The expression of granulocyte - macrophage colony - stimulating factor（GM - CSF） and tumor necrosis factor- α（TNF - α） were determinated by immunohistochemistry staining. The gene expression of NF - KB determined by real - time fluorescent quantitative PCR technology. Results：After treated drugs for 13 weeks, elimating phlegm group and nourishing qi group could reduce the lipid core as well as the ratio lipid to collagen content in plaque, but activating blood group only could reduce the ratio of lipids to collagen content in plaque. The positive expressions of GM - CSF in plaque on all the drug - treated groups were decreased significantly than controls, but the expression of TNF-α on all the groups had no difference with controls. Only the gene expression