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目的:观察祛痰方、化瘀方和祛痰化瘀方对高脂饮食导致的apo E~(-/-)小鼠全身和主动脉血管局部免疫反应的影响。方法:12周龄雄性apo E~(-/-)小鼠给予高脂饮食,治疗组同时给予基础方、祛痰方、化瘀方或祛痰化瘀方干预。4周后,检测血脂水平、外周血粒、单核细胞比例及其表面受体TLR4的表达;检测主动脉病理变化和细胞因子表达水平;进一步采用LPS刺激检测血浆细胞因子的水平。结果:4周高脂饮食导致apo E~(-/-)小鼠外周血TC和LDL水平显著增高;粒和单核细胞比例及其TLR4的表达显著升高;LPS刺激后,IL-12、TNF-α和MCP-1水平显著升高;主动脉组织不仅MCP-1、IL-1β和IL-6表达显著升高,IL-10也显著升高,Arg-1显著降低。4周的中药干预并未引起血脂明显改善,但祛痰化瘀方降低外周血粒细胞比例;对于LPS刺激高脂饲喂apo E-/-小鼠,基础方和活血化瘀方降低IL-12表达水平;对于主动脉血管局部,基础方降低主动脉血管IL-1β和IL-6表达,提高Arg-1表达;祛痰方显著抑制MCP-1、IL-1β和IL-6表达,而对抑炎因子无明显作用;活血化瘀方降低MCP-1、IL-1β和IL-6表达,提高IL-10和Arg-1表达;祛痰化瘀方仅抑制IL-1β表达,但提高IL-10、TGF-β和Arg-1表达。结论:高脂饮食引发apo E~(-/-)小鼠全身性炎症反应和血管局部炎症反应。中药祛痰方、化瘀方及祛痰化瘀方通过不同免疫调节机制,以独立于降脂作用的方式调节高脂血症引发的血管局部免疫反应。
Objective: To observe the effect of Qutanfang, Huayu Recipe and Qutan Huayu Recipe on systemic and aortic local immune responses in apo E ~ (- / -) mice induced by high fat diet. Methods: A 12-week-old male apo E ~ (- / -) mice were given a high-fat diet. The treatment group was also given the basic prescription, expectorant side, Huayu Recipe or Qutan Huayu Recipe intervention. After 4 weeks, the level of blood lipids, the ratio of peripheral blood monocytes and monocytes and the expression of TLR4 on their surface were detected; the pathological changes of aorta and the expression of cytokines were detected; and the levels of cytokines in plasma were detected by LPS stimulation. Results: After 4 weeks of high-fat diet, the level of TC and LDL in peripheral blood of apo E ~ (- / -) mice was significantly increased; the ratio of granulocytes and monocytes and the expression of TLR4 were significantly increased; The levels of TNF-α and MCP-1 in the aorta tissue were significantly increased. The expressions of MCP-1, IL-1β and IL-6 in aortic tissue were significantly increased, IL-10 was also significantly increased and Arg-1 was significantly decreased. 4 weeks of Chinese medicine intervention did not cause significant improvement in blood lipids, but expelling phlegm and resolving stasis to reduce the proportion of peripheral blood neutrophils; for LPS-stimulated apoE - / - mice fed high-fat, Fufang and Huoxue Huayu prescription reduce IL- 12 expression level. For aorta, the basal side decreased the expression of IL-1β and IL-6 in aorta and increased the expression of Arg-1. Expectorant side significantly inhibited the expression of MCP-1, IL-1β and IL-6 There was no significant effect of anti-inflammatory cytokines on the expression of IL-10 and Arg-1 in Huoxuehuayu Recipe. Activating blood circulation and removing blood stasis recipe could reduce the expression of MCP-1, IL-1β and IL-6, IL-10, TGF-β and Arg-1 expression. Conclusion: The high-fat diet induces the systemic inflammation and local inflammation in apo E ~ (- / -) mice. Traditional Chinese medicine expectorant side, Huayu Fang and expectorant Huayu prescription through different immune regulatory mechanisms, independent of the role of lipid-lowering effect of hyperlipidemia-induced local vascular immune response.