| 组蛋白去乙酰化酶2的表达在烟草烟雾暴露后哮喘大鼠气道Th1/Th2平衡中的作用研究 |
| 投稿时间：2016-09-07 修订日期：2016-09-30 点此下载全文 |
| 引用本文：李毅,熊雪,杜永成,许建英.组蛋白去乙酰化酶2的表达在烟草烟雾暴露后哮喘大鼠气道Th1/Th2平衡中的作用研究[J].医学研究杂志,2017,46(5):70-74 |
| DOI：
10.11969/j.issn.1673-548X.2017.05.019 |
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| 基金项目:山西省青年科技研究基金资助项目（2014021040-2） |
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| 中文摘要:目的 通过研究烟草烟雾暴露对哮喘大鼠气道组蛋白去乙酰化酶（histone deacetylase，HDAC）2以及血浆、支气管肺泡灌洗液（BALF）中干扰素（interferon，IFN）-γ、白细胞介素（interleukin，IL）-4表达的影响，探讨HDAC2在辅助性T淋巴细胞（T helper cell）Th1/Th2平衡中的作用。方法 50只雄性Wistar大鼠随机分为对照组、哮喘组、烟雾暴露+哮喘组、布地奈德+哮喘组、布地奈德+烟雾暴露+哮喘组，建立哮喘大鼠模型、哮喘大鼠烟雾暴露模型以及布地奈德干预模型。免疫组织化学法检测各组大鼠气道HDAC2蛋白的表达，酶联免疫吸附试验法（ELISA）检测血浆和BALF中Th1型特征性细胞因子IFN-γ以及Th2型特征性细胞因子IL-4水平。结果 与对照组相比，烟雾暴露+哮喘组、哮喘组大鼠气道HDAC2蛋白表达降低，与哮喘组相比，烟雾暴露+哮喘组大鼠气道HDAC2蛋白表达降低，差异均有统计学意义（P均<0.05）。与布地奈德+哮喘组相比，布地奈德+烟雾暴露+哮喘组大鼠气道HDAC2蛋白表达降低，差异有统计学意义（P<0.05）；与对照组相比，哮喘组大鼠和烟雾暴露+哮喘组大鼠血浆、BALF中IFN-γ表达减少，IL-4表达增加，差异均有统计学意义（P均<0.01）；与哮喘组相比，烟雾暴露+哮喘组大鼠血浆、BALF中IFN-γ表达减少，IL-4表达增加，差异均有统计学意义（P均<0.01）；与布地奈德+哮喘组相比，布地奈德+烟雾暴露+哮喘组大鼠血浆、BALF中IFN-γ表达减少，IL-4表达增加，差异均有统计学意义（P均<0.01）；肺组织HDAC2蛋白的表达与血浆中IFN-γ表达呈正相关（r=0.533，P<0.01），与IL-4表达呈负相关（r=-0.642，P<0.01）。结论 烟草烟雾暴露可以下调哮喘大鼠模型肺组织HDAC2蛋白的表达，从而影响气道炎症，IFN-γ、IL-4的表达以及布地奈德的治疗效果，这可能是烟草烟雾恶化哮喘气道Th 1/Th2平衡的一个免疫学机制。 |
| 中文关键词:烟草烟雾暴露 支气管哮喘 组蛋白去乙酰化酶2 免疫机制 |
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| Role of HDAC2 on Th1/Th2 balance in asthmatic rats with cigarette smoke exposure |
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| Abstract:Objective To study the effect of cigarette smoke exposure on the expression of histone deacetylase (HDAC)2,interferon(IFN)-γ and interleukin(IL)-4,and to explore immunological mechanism of Th1/Th2 imbalance about cigarette smoke exposure aggravating asthma. Methods Fifty 50 healthy male Wistar rats were divided randomly into control group, asthma group,cigarette smoke exposure combined asthma group.Asthma group was treated by budesonide,cigarette smoke exposure combined asthma group treated by budesonide. We established the rats model of every group.The expression of HDAC2 protein was determined by immunohistochemistry and IFN-γ、IL-4 in peripheral blood and bronchoalveolar lavage fluid(BALF)were measured by enzyme-linked immunosorbent assay (ELISA). Results Compared with the control group,the expression of HDAC2 protein increased remarkably in the asthma group and the cigarette smoke exposure combined asthma group(P<0.01,respectively).Compared with the asthma group,the expression of HDAC2 protein increased remarkably in the cigarette smoke exposure combined asthma group(P<0.01).Compared with the asthma group treated by budesonide,the expression of HDAC2 protein increased remarkably in the cigarette smoke exposure combined asthma group treated by budesonide(P<0.01).Compared with the control group,IFN-γ of peripheral blood and BALF decreased and IL-4 increased remarkably in the asthma group and the cigarette smoke exposure combined asthma group(P<0.01).Compared with the asthma group,IFN-γ of peripheral blood and BALF decreased and IL-4 increased remarkably in the cigarette smoke exposure combined asthma group(P<0.01).Compared with the asthma group treated by budesonide,IFN-γ of peripheral blood and BALF decreased and IL-4 increased remarkably in the cigarette smoke exposure combined asthma group treated by budesonide(P<0.01).The expression of HDAC2 protein was positively correlated with IFN-γ of peripheral blood and BALF and was negatively correlated with IL-4 of peripheral blood and BALF. Conclusion Cigarette smoke exposure can down-regulate the expression of HDAC2 protein,IFN-γ,and up-regulate the expression of IL-4,which may play an important role in aggravating airway inflammation and Th1/Th2 balance in asthmatic rats. |
| keywords:Smoke exposure Asthma HDAC2 Immune mechanism |
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