清热化痰活血方药稳定ApoE基因敲除小鼠主动脉易损斑块及与蛋白酶体通路的关系

发布时间：2018-09-06 18:09

【摘要】：目的:观察清热化痰活血方对Apo E基因敲除小鼠主动脉粥样硬化易损斑块的稳定作用及对泛素通路的影响。方法:Apo E基因敲除小鼠80只,自8周龄时予以高脂饮食,随机分为空白对照组、蛋白酶体抑制剂组、蛋白酶体抑制剂加清热化痰活血方组及清热化痰活血方组,每组20只。自13周始给药,分别给予0.9%氯化钠溶液10mg·kg-1·d-1,硼替佐米3.0mg·kg-1·d-1,硼替佐米3.0mg·kg-1·d-1加清热化痰活血方180mg·kg-1·d-1及清热化痰活血方180mg·kg-1·d-1,17周后评估主动脉病理形态学改变,免疫荧光法测定主动脉斑块中单核细胞/巨噬细胞-2(MOMA-2)的表达、免疫组化法测定NF-кB的P65亚基的表达及CD40L表达,荧光探针的方法测定超氧化物阴离子自由基的表达。结果:蛋白酶体抑制剂加清热化痰活血方组与蛋白酶体抑制剂组比较主动脉的MOMA-2的荧光表达、CD40L的表达、NF-кB的P65亚基的表达、超氧化物阴离子自由基的表达均无显著变化,但斑块的脂质核含量有显著下降(P0.01);清热化痰活血方组与其他各组比较,主动脉的MOMA-2的荧光表达、NF-кB的P65亚基及CD40L的表达、超氧化物阴离子自由基及CD40L的表达、斑块的脂质核含量均有显著下降(P0.01)。结论:清热化痰活血方可以显著抑制主动脉动脉粥样硬化的炎性因子的表达,其机制与部分抑制泛素蛋白酶体通路有关,蛋白酶体可能是中药作用的一个靶点。
[Abstract]:Aim: to observe the stabilizing effect of Qingre Huatan Huoxue recipe on atherosclerotic plaque in Apo E knockout mice and its effect on ubiquitin pathway. Methods Eighty mice with 1% Apo E gene knockout were randomly divided into three groups: control group, proteasome inhibitor plus Qingre Huatan Huoxue recipe group and Qingre Huatan Huoxue recipe group, with 20 rats in each group. After 13 weeks of administration, 10mg kg-1 d-1, 3.0mg kg-1 d-1, 180mg kg-1 d-1 and 180mg kg-1 d-1, respectively, were administered with 0.9% sodium chloride solution for 17 weeks to evaluate the pathological changes of aorta. The expression of monocyte / macrophage -2 (MOMA-2) in aortic plaques was detected by immunofluorescence, the expression of p65 subunit and CD40L of NF- B was detected by immunohistochemistry, and the expression of superoxide anion free radical was detected by fluorescence probe method. Results: compared with proteasome inhibitor group and proteasome inhibitor group, the expression of CD40L in aorta and the expression of P65 subunit of NF- B were not significantly changed in comparison with those in proteasome inhibitor group. Compared with other groups, the fluorescence expression of MOMA-2 in aorta and the expression of P65 subunit and CD40L of NF-B, superoxide anion radical and CD40L expression in aorta were significantly decreased (P0.01), and the expression of superoxide anion free radical and CD40L were also observed in the group of Qingre Huatan Huoxue recipe, the expression of P65 subunit of NF-B and the expression of CD40L in aorta. The content of lipid nuclei in plaque decreased significantly (P0.01). Conclusion: Qingre Huatan Huoxue recipe can significantly inhibit the expression of inflammatory factors in atherosclerosis of aorta, and its mechanism is related to partial inhibition of ubiquitin proteasome pathway. Proteasome may be a target of Chinese medicine.
【作者单位】：中日友好医院心内科;北京中医药大学;中日友好医院临床医学研究所;
【基金】：国家自然科学基金(No.81173420)~~
【分类号】：R285.5

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