参芪补肺汤对慢性阻塞性肺疾病大鼠支气管平滑肌增殖中乙酰化组蛋白H4和NF-κBp65表达的影响

来源 :贵阳中医学院学报 | 被引量 : 0次 | 上传用户:zgymm2008
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目的:观察参芪补肺汤对慢性阻塞性肺疾病(COPD)肺气虚证大鼠支气管平滑肌(ASM)增殖中乙酰化组蛋白H4和NF-κBp65表达的影响。方法:将40只SD大鼠随机分为正常组、中药组、氨茶碱组、模型组,每组各10只。采用气管内滴注脂多糖加烟熏28天的方法建立COPD肺气虚证大鼠模型。光镜下观察肺组织的病理形态学变化,运用图像分析法测量小气道管壁和ASM的厚度,采用免疫组化和蛋白质印迹法(Western blot)检测大鼠ASM中乙酰化组蛋白H4的表达。采用免疫组化、实时荧光定量PCR和Western blot方法检测大鼠ASM中NF-κBp65的表达。结果:与正常组比较,模型组大鼠气道管壁和ASM的厚度明显增厚(P<0.05),乙酰化组蛋白H4的蛋白表达与NF-κBp65mRNA和蛋白的表达明显增高(P<0.05),中药组与氨茶碱组比较差异均无统计学意义(P>0.05)。与模型组比较,中药组和氨茶碱组大鼠小气道管壁和ASMC的厚度均明显降低(P<0.05),乙酰化组蛋白H4的蛋白表达与NF-κBp65mRNA和蛋白的表达均明显降低(P<0.05),中药组与氨茶碱组比较差异均无统计学意义(P>0.05)。结论:参芪补肺汤可抑制COPD肺气虚证模型大鼠ASM增殖,其机制与通过降低乙酰化组蛋白H4的表达,从而抑制NF-κBp65表达有关。 Objective: To observe the effect of Shenqibufei decoction on the expression of histone H4 and NF-κB p65 in the proliferation of bronchial smooth muscle (ASM) in rats with chronic obstructive pulmonary disease (COPD). Methods: Forty SD rats were randomly divided into normal group, TCM group, aminophylline group and model group, with 10 rats in each group. Adopting intratracheal instillation of lipopolysaccharide and smoked for 28 days, a rat model of COPD with lung-qi deficiency syndrome was established. The pathological changes of lung tissue were observed under light microscope. The thickness of small airway wall and ASM were measured by image analysis. The expression of acetylated histone H4 in ASM was detected by immunohistochemistry and Western blot . The expression of NF-κBp65 in rat ASM was detected by immunohistochemistry, real-time fluorescence quantitative PCR and Western blot. Results: Compared with normal group, the thickness of airway wall and ASM in model group was significantly thicker (P <0.05), the expression of acetylated histone H4 protein and NF-κBp65 mRNA and protein were significantly increased (P <0.05 ), There was no significant difference between the traditional Chinese medicine group and the aminophylline group (P> 0.05). Compared with model group, the thickness of small airway wall and ASMC in Chinese medicine group and aminophylline group were significantly decreased (P <0.05), the expression of acetylated histone H4 protein and NF-κBp65 mRNA and protein were significantly decreased (P <0.05). There was no significant difference between the traditional Chinese medicine group and the aminophylline group (P> 0.05). Conclusion: Shenqibufei decoction can inhibit the proliferation of ASM in COPD model rats with lung-qi deficiency, and its mechanism is related to decreasing the expression of acetylated histone H4, thereby inhibiting the expression of NF-κBp65.
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