参芪补肺汤对慢性阻塞性肺疾病肺气虚证大鼠气道平滑肌中乙酰化组蛋白H4、HDAC2和NF-μB p65表达的影响  

Effects of Shenqi Bufei Decoction on Expression of Acetylated Histone H4, Histone deace-tylase-2 and Nuclear Factor-κB p65 in Airway Smooth Muscle of Chronic Obstructive Pulmonary Disease Rat Model with Lung-Qi Deficiency Syndrome.

作　　者：吴桂英[1] 张葵[1] 闫萍[1] 周佐涛[1] 李琼[1] 张纯娟[1] 万晓春[1] 费小强[2] 

机构地区：[1]贵州省人民医院,贵州贵阳550002 [2]贵阳中医学院第一附属医院,贵州贵阳550001

出　　处：《中药新药与临床药理》2014年第6期688-693,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金(81160450);贵州省科技计划项目(黔科合SY字2012-3142)

摘　　要：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)中乙酰化组蛋白H4、组蛋白去乙酰化酶-2(HDAC2)和核因子-κB p65(NF-κB p65)表达的影响。方法取SD大鼠40只,随机分为正常组、模型组、参芪补肺汤组、氨茶碱组,每组10只。运用气管内注射脂多糖加烟熏28 d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Western blot方法检测大鼠ASM中乙酰化组蛋白H4、HDAC2和NF-κB p65的蛋白表达,实时荧光定量PCR方法检测大鼠ASM组织中HDAC2 m RNA和NF-κB p65 m RNA的表达。结果与正常组比较,模型组大鼠气道管壁和ASM厚度明显增高(P<0.05);与模型组比较,参芪补肺汤组和氨茶碱组气道管壁和ASM厚度明显降低(P<0.05);参芪补肺汤组与氨茶碱组比较差异无统计学意义(P>0.05)。与正常组比较,模型组乙酰化组蛋白H4的蛋白表达、NF-κB p65 m RNA和蛋白的表达明显增高(P<0.05);HDAC2m RNA和蛋白的表达均明显降低(P<0.05);与模型组比较,参芪补肺汤组和氨茶碱组乙酰化组蛋白H4的蛋白表达、NF-κB p65 m RNA和蛋白的表达明显增高(P<0.05);HDAC2 m RNA和蛋白的表达明显降低(P<0.05)。参芪补肺汤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,其机制与其提高HDAC2的表达,使组蛋白H4去乙酰化,从而抑制NF-κB p65的表达有关。Objective To observe the effects of She nqi Bufei Decoction（SBD）on expession of acetylated histone H4,histone deace-tylase-2（HDAC2） and nuclear factor-κB p65（NF-κB p65） in the airway smooth muscle of chronic obstructive pulmonary disease（COPD） rat model with lung-Qi deficiency syndrome. Methods Forty male rats were randomly divided into normal group, model group, SBD group, aminophylline group. The rat model with lung-Qi deficiency syndrome of COPD was established by intratracheal instillation of lipopolysaccharide（LPS） combined with passive smoking for 28 days. Image analysis was used to measure the airway smooth muscle（ASM）layer thickness of small airway after examination under light microscope. Immunohistochemistry and Western blotting were applied to detect the expression of acetylated histone H4, NF-κB p65 and HDAC2 in rat bronchial smooth muscle tissue.Real-time fluorescent quantitation PCR was used to detect the expression of HDAC2 m RNA and NF-κB p65 m RNA in ASM tissue of rats. Results Compared with the normal group, the thickness of airway wall and ASM were obviously increased in the model group（P〈0.05）. Compared with the model group,the thickness of airway wall and ASM were obviously decreased in SBD group and aminophylline group（P〈0.05）, the difference between SBD group and aminophylline group being insignificant（P〈0.05）. Compared with the normal group, expression levels of acetylated histone H4 protein and NF-κB p65 m RNA and protein were significantly increased in the model group（P〈0.05）,while the expression levels of HDAC2 m RNA and protein were significantly decreased（P〈0.05）. After treatment with SBD or aminophylline, the expression levels of the above indexes were counteracted（P〈0.05）, and the effect of SBD was similar to aminophylline（P〉0.05）. Conclusion She nqi Bufe i Decoction can inhibit bronchial smooth muscle proliferation in rats with COPD of lung-Qi deficiency syndrome,and its mechanisms may be related to the increase

关 键 词：慢性阻塞性肺疾病 气道平滑肌 乙酰化组蛋白H4 组蛋白去乙酰化酶-2 核因子-ΚBP65 

分 类 号：R285.5[医药卫生—中药学]