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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(P<0.01);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(P<0.01)。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。
Objective: To observe the effect of clearing away heat, removing phlegm and activating blood prescription on the stability of vulnerable plaque of ApoE gene knockout mice and its influence on ubiquitin pathway. Methods: Eighty Apo E knock-out mice were randomly divided into blank control group, proteasome inhibitor group, proteasome inhibitor plus Qingre Huatan Huoxue Recipe group and Qingre Huatan Decoction group Blood group, each group of 20. Patients were given 0.9% sodium chloride solution 10 mg · kg-1 · d-1, bortezomib 3.0 mg · kg-1 · d-1, bortezomib 3.0 mg · kg-1 · d -1 plus Qingre Huatanhuoxue 180mg · kg-1 · d-1 and Qingre Huatan Huoxue 180mg · kg-1 · d-1,17 weeks after the assessment of aortic pathological changes, immunofluorescence method for the determination of the aorta The expression of monocyte / macrophage-2 (MOMA-2) was detected by immunohistochemistry. The expression of P65 subunit of NF-кB and the expression of CD40L were detected by immunohistochemistry. The superoxide anion free radical expression. Results: The expression of MOMA-2, the expression of CD40L, the expression of P65 subunit of NF-κB, the superoxide anion free radical (P <0.01). Compared with the other groups, the expression of MOMA-2 in the aorta and the expression of NF-кB in the aorta of Qingre Huatan Huoxue Recipe group were significantly decreased P65 subunit and CD40L expression, superoxide anion free radical and CD40L expression, plaque lipid core content were significantly decreased (P <0.01). Conclusion: The heat-clearing, resolving phlegm and activating blood circulation can significantly inhibit the expression of inflammatory factors in aortic atherosclerosis. Its mechanism is related to the partial inhibition of ubiquitin proteasome pathway. Proteasome may be a target of traditional Chinese medicine.