[1]孙盼锋,张 辉,黄仕夫,等.克拉霉素联合布地奈德对COPD大鼠糖皮质激素抵抗的影响[J].郑州大学学报(医学版),2017,(03):322-325.[doi:10.13705/j.issn.1671-6825.2017.03.020]
 SUN Panfeng,ZHANG Hui,HUANG Shifu,et al.Effect of clarithromycin and budesonide on glucocorticoid resistance in COPD rats[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2017,(03):322-325.[doi:10.13705/j.issn.1671-6825.2017.03.020]
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克拉霉素联合布地奈德对COPD大鼠糖皮质激素抵抗的影响()
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《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2017年03期
页码:
322-325
栏目:
应用研究
出版日期:
2017-05-15

文章信息/Info

Title:
Effect of clarithromycin and budesonide on glucocorticoid resistance in COPD rats
作者:
孙盼锋张 辉黄仕夫黄凤祥赵 娣苗丽君#
郑州大学第一附属医院呼吸内科 郑州 450052
Author(s):
SUN PanfengZHANG HuiHUANG ShifuHUANG FengxiangZHAO DiMIAO Lijun
Department of Respiratory Disease,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052
关键词:
克拉霉素 布地奈德 慢性阻塞性肺疾病 糖皮质激素抵抗 糖皮质激素受体 大鼠
Keywords:
clarithromycin budesonide chronic obstructive pulmonary disease glucocorticoid resistance glucocorticoid receptor rat
分类号:
R563.9
DOI:
10.13705/j.issn.1671-6825.2017.03.020
摘要:
目的:探讨克拉霉素联合布地奈德对慢性阻塞性肺疾病(COPD)大鼠糖皮质激素抵抗的影响。方法:对大鼠进行COPD造模,然后分4组处理,COPD组、克拉霉素组、布地奈德组和联合干预组(克拉霉素+布地奈德组),每组10只; 以10只未处理未造模大鼠作空白对照(空白组)。留取各组大鼠肺组织和血清,HE染色,光镜下观察肺组织病理学改变,采用ELISA法测定血清中TNF-α水平,采用RT-PCR及Western blot检测肺组织糖皮质激素受体α(GRα)及GRβ的表达。结果:与空白组相比,COPD组大鼠气管及支气管黏膜上皮细胞脱落,炎性细胞浸润,支气管平滑肌增厚,肺泡壁变薄,甚至破裂融合成肺大泡,血清TNF-α水平升高,提示造模成功。对COPD组、克拉霉素组、布地奈德组和联合干预组的分析表明,克拉霉素和布地奈德均可降低COPD大鼠血清TNF-α水平和肺组织GRβ mRNA和蛋白的表达水平,升高肺组织GRα mRNA和蛋白的表达水平,且二者联用有协同作用(P<0.05)。结论:克拉霉素、布地奈德均可在不同程度上调节GRα/GRβ失衡,从而改善COPD大鼠糖皮质激素抵抗,二者联用抗炎效果更佳。
Abstract:
Aim: To explore the effect of clarithromycin and budesonide on chronic obstructive pulmonary disease(COPD)rat glucocorticoid resistance and its mechanism.Methods: Rats were randomly allocated into 5 groups, blank group,COPD group,clarithromycin group,budesonide group, and combined intervention group; 10 rats in each group.The rats in the latter 4 groups were made COPD model. The pathological changes of lung tissue were observed by HE staining. Level of TNF-α in serum was determined by ELISA. The expressions of glucocorticoid receptor α(GRα)and GRβ mRNA and protein in lung tissue were detected by RT-PCR and Western blot.Results: Compared with blank group, there were tracheal and bronchial epithelial cells shedding, inflammatory cell infiltration, thickening of bronchial smooth muscle, alveolar wall thinning or even ruptured and fused into bullae of lung,and the level of serum TNF-α increased in COPD group(P<0.05). Compared with COPD group,the level of serum TNF-α and the expressions of GRβ mRNA and protein decreased in clarithromycin group and budesonide group, while those of GRα mRNA and protein increased(P<0.05),and the 2 drugs had synergistic effects(P<0.05).Conclusion: Clarithromycin or budesonide could adjust GRα/GRβ imbalance,reverse glucocorticoid resistance in COPD rats,and the antiinflammatory effect is synergistic when they are combined.

参考文献/References:

[1] 佚名.2016GOLD:COPD 诊断、治疗与预防全球策略(更新版)[J].中国全科医学,2016,19(5):524
[2] ARORA VK,SCHENKEIN E,MURALI R,et al.Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade[J].Cell,2013,155(6):1309
[3] GEER EB,ISLAM J,BUETTNER C.Mechanisms of glucocorticoid-induced insulin resistance: focus on adipose tissue function and lipid metabolism[J].Endocrinol Metab Clin North Am,2014,43(1):75
[4] HERATH SC,POOLE P.Prophylactic antibiotic therapy in chronic obstructive pulmonary disease[J].JAMA,2014,311(21):2225
[5] AMMIT AJ.Glucocorticoid insensitivity as a source of drug targets for respiratory disease[J].Curr Opin Pharmacol,2013,13(3):370
[6] ZHENG H,LIU Y,HUANG T,et al.Development and characterization of a rat model of chronic obstructive pulmonary disease(COPD)induced by sidestream cigarette smoke[J].Toxicol Lett,2009,189(3):225
[7] 高增艳.红霉素对COPD大鼠组蛋白云乙酰化酶2活性与糖皮质激素抵抗的影响及机制[D].郑州:郑州大学,2013.
[8] KEENAN CR,LEW MJ,STEWART AG.Biased signalling from the glucocorticoid receptor:Renewed opportunity for tailoring glucocorticoid activity[J].Biochem Pharmacol,2016,112:6
[9] BASYIGIT I,YILDIZ F,OZKARA K,et al.The effect of clarithromycin on inflammatory markers in chronic obstructive pulmonary disease: preliminary data[J].Ann Pharmacother,2004,38(9):1400

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备注/Memo

备注/Memo:
*河南省科技厅攻关项目 162102310196
#通信作者,女,1970年5月生,博士,教授,主任医师,研究方向:呼吸系统疑难疾病的基础与临床、肺癌的发病机制与治疗,E-mail:miaolily@126.com
更新日期/Last Update: 2017-05-20