摘要
目的探究PM_(2.5)是否通过组蛋白乙酰化途径加重大鼠哮喘。方法选择雄性SD大鼠45只,随机分为5组,分别为生理盐水对照组、哮喘组、PM_(2.5)低、中、高剂量刺激哮喘组。采用qRT-PCR、Western blot方法分别检测HDAC1、HDAC2 mRNA及蛋白表达水平,ELISA、免疫组织化学法测定组蛋白H3K9、H3K18乙酰化水平。结果 PM_(2.5)中、高剂量刺激哮喘组HDAC2 mRNA水平、PM_(2.5)中剂量刺激哮喘组HDAC1蛋白表达量、PM_(2.5)高剂量刺激哮喘组HDAC2蛋白表达量均低于哮喘组(P<0.05)。PM_(2.5)低、中、高剂量刺激哮喘组H3K9ac水平高于哮喘组(P<0.05),PM_(2.5)高剂量刺激哮喘组H3K18ac水平高于哮喘组、PM_(2.5)低、中剂量刺激哮喘组(P<0.05);H3K9ac、H3K18ac蛋白表达主要集中在支气管上皮细胞,哮喘组表达量高于生理盐水对照组(P<0.05);PM_(2.5)中、高剂量刺激哮喘组高于哮喘组(P<0.05)。结论 PM_(2.5)可能通过降低HDAC2基因和HDAC1、HDAC2蛋白的表达,使组蛋白H3K9、H3K18乙酰化水平升高,从而加重大鼠哮喘。
Objective To investigate whether the asthma in rats aggravated by PM（2.5） was mediated by histone acetylation pathway. Methods Forty-five male Sprague-Dawley rats were randomly divided into five groups： one normal saline group,one asthma group（ stimulated by OVA） and three PM（2.5） asthma groups（ stimulated by low,medium and high doses of PM（2.5） and OVA）. The levels of HDAC1 and HDAC2 mRNA and protein were detected by qRT-PCR and Western blot respectively. The levels of H3 K9 and H3 K18 were measured by ELISA and immunohistochemistry. Results The level of HDAC2 mRNA in medium and high dose PM（2.5） asthma groups,the expression of HDAC1 protein in medium dose PM（2.5） asthma group and the expression of HDAC2 protein in high dose PM（2.5） asthma group were lower than that in asthma group（ P 0. 05）. The level of H3 K9 ac in low,medium and high dose PM（2.5） asthma group were higher than that in asthma group,the level of H3 K18 ac in high dose PM（2.5） asthma group was higher than that in asthma group and low and medium dose PM（2.5） asthma groups（ P 0. 05）. The expression of H3 K9 ac,H3 K18 ac protein was mainly concentrated in bronchial epithelial cells,and the expression in asthma group was higher than that in saline control group（ P 0. 05）; the expression in medium and high dose PM（2.5） asthma groups was higher than that in asthma group（ P 0. 05）. Conclusion By means of decreasing the expression of HDAC2 gene and HDAC1 and HDAC2 protein,PM（2.5） might increase the acetylation of histone H3 K9 and H3 K18,thus aggravate asthma in rats.
出处
《环境卫生学杂志》
2017年第5期337-342,共6页
JOURNAL OF ENVIRONMENTAL HYGIENE
基金
教育部留学回国人员科研启动基金(教外司留2013-1792号)
山西省回国留学人员科研资助项目(2013-057)
