茶碱联合红霉素对慢性阻塞性肺疾病大鼠炎症介质及HDAC-2的影响  

Effect of Theophylline Combined with Erythromycin on the inflammatory Mediators and HDAC-2 of Chronic Obstructive Pulmonary Disease in Rats

作　　者：高少勇[1] 金咏絮[1] 连宁芳[1] 林其昌[1] 陈公平[1] GAO Shaoyong;JIN Yongxu;LIAN Ningfang;LIN Qichang;CHEN Gongping(Department of Respiratory and Critical Care Medicine,The First AffiliatedHospital of Fujian Medical University,Fuzhou 350005,China)

机构地区：[1]福建医科大学附属第一医院呼吸与危重症医学科

出　　处：《福建医科大学学报》2019年第2期80-84,共5页Journal of Fujian Medical University

基　　金：福建省卫生与计划生育委员会青年基金(2015-1-52)

摘　　要：目的探讨茶碱联合红霉素对慢性阻塞性肺疾病(COPD)大鼠的抗炎作用及对组蛋白去乙酰化酶2(HDAC-2)的影响。方法雄性SD大鼠50只,随机分为正常组(n=10)和COPD组(n=40),COPD组再分为对照组、红霉素组、茶碱组及红霉素+茶碱组,每组各10只。取各组大鼠的肺组织和血清,H-E染色检测肺组织的病理学改变,ELISA法检测血清及肺泡液中白细胞介素-8(IL-8)和肿瘤坏死因子α(TNF-α)水平,免疫组织化学法检测肺组织HDAC-2的表达。结果与正常组比较,对照组大鼠气管及支气管黏膜上皮细胞脱落,支气管平滑肌增厚,肺泡壁变薄,炎性细胞浸润,血清及肺泡液中的IL-8及TNF-α水平均显著上升,而肺组织中HDAC-2表达水平显著下降(P<0.05);与对照组比较,红霉素组和茶碱组大鼠血清及肺泡液的IL-8及TNF-α水平均显著下降,而肺组织中的HDAC-2表达水平显著上升(P<0.05);与红霉素组及茶碱组比较,红霉素+茶碱组大鼠血清及肺泡液中的IL-8及TNF-α水平均显著降低(P<0.05),而肺组织中的HDAC-2表达水平显著升高(P<0.05)。结论红霉素和茶碱均可有效减轻COPD大鼠的炎症反应,上调肺组织的HDAC-2表达水平,改善糖皮质激素抵抗,二者联合应用效果更好。Objective To investigate the anti-inflammatory effects of theophylline combined with erythromycin onHDAC-2 in COPD rats.MethodsForty male SD rats were randomly divided into COPD group, which consisted of control group, erythromycin group, theophylline group, and erythromycin + theophylline group, with 10 rats in each group.In addition, 10 untreated non-model rats were in a normal control group.The lung tissue and serum of rats in each group were collected and stained with hematoxylin and eosin (H-E).The pathological changes of lung tissue were observed under light microscope.ELISA was performed to analyze the levels of interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-α).The expression of histone deacetylase 2 (HDAC-2) in lung tissue was detected by immunohistochemistry.ResultsCompared with the normal rat group, the tracheal and bronchial epithelial cells of the control group were exfoliated, the bronchial smooth muscle was thickened, the alveolar wall became thinner, the inflammatory cells infiltrated, and the levels of serum and alveolar fluid IL-8 and TNF-α in the control group were higher, while the level of HDAC-2 in lung tissue decreased significantly ( P<0.05 ).Compared with the control group, the levels of IL-8 and TNF-α in serum and alveolar fluid in erythromycin group and theophylline group were significantly reduced, while the expression of HDAC-2 in lung tissue increased significantly ( P<0.05).The levels of IL-8 and TNF-α in serum and alveolar fluid in erythromycin + theophylline group were significantly lower than those in erythromycin group or in theophylline group ( P<0.05), and the expression level of HDAC-2 in lung tissue was significantly higher than that in erythromycin group and theophylline group ( P <0.05).ConclusionErythromycin or theophylline can effectively reduce the inflammatory response in COPD rats, upregulate the expression of HDAC-2 in lung tissue, and the combined effect is better.

关 键 词：肺疾病 慢性阻塞性 组蛋白类 白细胞介素8 肿瘤坏死因子Α 

分 类 号：R322[医药卫生—人体解剖和组织胚胎学] R341.27[医药卫生—基础医学]