摘要
目的明确哮喘大鼠肺T淋巴细胞中的组蛋白去乙酰基酶1(HDAC1)蛋白表达水平及组蛋白整体乙酰化和甲基化水平,探讨其在哮喘发病机制中的作用。方法 16只Wistar大鼠随机分为对照组和哮喘组(每组8只),用卵白蛋白(OVA)致敏并激发建立哮喘大鼠模型。通过哮喘临床表现、气道高反应性测定、肺组织HE染色、血清和BALF中细胞因子IL-4、γ干扰素(IFN-γ)及IgEELISA测定,判断哮喘大鼠模型是否成功。分离肺T细胞并进行纯度鉴定。Western blot检测肺T细胞HDAC1蛋白表达水平,组蛋白H3、H4整体乙酰化,以及H3k9整体二甲基化水平。结果与对照组比较,哮喘组HDAC1蛋白表达水平低于对照组(P<0.05),组蛋白H3、H4整体乙酰化水平和H3k9整体二甲基化水平差异均无统计学意义。结论肺T细胞HDAC1可能参与了支气管哮喘的发病环节,组蛋白整体乙酰化和甲基化水平与哮喘发病无明显相关性,HDAC1对组蛋白修饰作用可能是一个基因转录特异性事件。
Objective To investigate the expression of the histone deacetylases 1（HDAC1） and the level of whole histone acetylation and methylation in lung T cells of asthmatic rats,and investigate their role in the pathogenesis of asthma.Methods Sixteen wistar rats were randomly divided into a control group and an asthma group（n=8 in each group）.The rats was sensitized with ovalbumin（OVA） and challenged with aerosol OVA to establish asthma model.The asthmatic rat model was confirmed by measurement of pulmonary function,histochemical staining,HE staining,and the levels of interleukin-4（IL-4）,interferon-gamma（IFN-γ） and immunoglobulin E（IgE） in serum and bronchoalveolar lavage fluid（BALF）.T cells were isolated from rat lungs and the purity was identified.The expression of the HDAC1,the level of whole histone H3 and H4 acetylation,and whole H3K9 dimethylation were analyzed by Western blot in lung T cells.Results Compared with the control group,the protein expression of HDAC1 was significantly lower（0.465±0.087 vs 0.790±0.076,P0.05） in lung T cells of the asthma group.No significant differences were found in regard to the level of whole histone H3 and H4 acetylation and whole H3K9 dimethylation between the two groups.Conclusions HDAC1 in lung T cells may be involved in the pathogenesis of asthma.Histone modification by HDAC1 may be a specific event with gene transcription which may not be associated with asthma.
出处
《中国呼吸与危重监护杂志》
CAS
2010年第3期259-263,共5页
Chinese Journal of Respiratory and Critical Care Medicine
基金
国家自然科学基金(编号:30971302)
上海市教育委员会科研创新重点项目(编号:09ZZ114)
