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特异性p38丝裂原活化蛋白激酶抑制剂对哮喘气道黏液高分泌的抑制作用
  • ISSN号:0577-7402
  • 期刊名称:《解放军医学杂志》
  • 时间:0
  • 分类:R562.25[医药卫生—呼吸系统;医药卫生—临床医学;医药卫生—内科学]
  • 作者机构:[1]第四军医大学西京医院呼吸内科,西安710032, [2]第四军医大学西京医院生物化学与分子生物学教研室, [3]第四军医大学西京医院病理教研室
  • 相关基金:国家自然科学基金面上项目(30400197)
中文摘要:

目的观察p38丝裂原活化蛋白激酶(p38 MAPK)特异性抑制剂SB203580对哮喘模型小鼠气道黏液高分泌的抑制作用。方法取BABL/C小鼠40只,按随机数字表法分为哮喘组、SB203580治疗组、地塞米松治疗组和正常对照组,每组10只。高碘酸希夫(AB-PAS)特染法检测各组小鼠小支气管杯状细胞的数量,ELISA法检测支气管肺泡灌洗液中黏蛋白MUC5AC含量,RT-PCR法检测小鼠肺组织MUC5AC mRNA表达水平,并采用图像分析法进行灰度分析。结果与正常对照组相比,哮喘组的上皮杯状细胞数量、支气管肺泡灌洗液中MUC5AC含量、肺组织MUC5AC mRNA表达水平均显著增加(P〈0.01)。经过SB203580和地塞米松分别干预后,上述指标均明显低于哮喘组(P〈0.01),而且SB203580对杯状细胞、肺组织MUC5AC mRNA的抑制能力比地塞米松更强(P〈0.01)。结论p38 MAPK特异性抑制剂SB203580在一定程度上能够抑制杯状细胞增生与MUC5AC合成,在哮喘气道黏液高分泌的防治中具有潜在的临床应用前景。

英文摘要:

Objective To explore the inhibitory effects of SB203580, a specific inhibitor of p38 mitogen activated protein kinase (p38 MAPK) on hyper secretion of airway mucus in mice with asthma. Methods Forty BABL/C mice were randomly allocated into asthma group, SB203580 treatment group, dexamethasone treatment group and control group (sham-challenged group). Mice in SB203580 treatment group were intraperitoneally injected with SB203580 (10mg/kg), while those in dexamethasone treatment group were injected with dexamethasone (1mg/kg) before provocation. The number of goblet cells in small bronchi of all groups was determined after Alcian blue-periodic acid Schiff (AB-PAS) staining. The contents of MUC5AC in bronchoalveolar lavarge fluid (BALF) were evaluated with ELISA asssy. The levels of MUC5AC mRNA expression were determined with reverse transcription-polymerase chain reaction (RT-PCR) assay, and gray-scale analysis was done with image analysis method. Results Compared with the normal group, the number of airway goblet cells, the contents of MUC5AC in BALF and the level of lung MUC5AC mRNA expression in asthma group were raised significantly (P〈0.01). The three indices in both SB203580 and dexamethasone treatment groups were lower than that in asthma group (P〈0.01). In addition, the number of airway goblet cells and the level of lung MUC5AC mRNA expression in SB20358 treatment group declined more obviously compared with that in dexamethasone treatment group (P〈0.01). Conclusions It can be demonstrated that SB203580, the specific inhibitor of p38 MAPK, may inhibit the proliferation of goblet cells and the synthesis of MUC5AC in mice with asthma, and the former has the strong suppressing effect on hyper secretion of airway mucus. So SB203580 may have a potential clinical perspective in the treatment of the patients with mucus hyper secretion induced by asthma.

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期刊信息
  • 《解放军医学杂志》
  • 中国科技核心期刊
  • 主管单位:中国人民解放军总后勤部卫生部
  • 主办单位:人民军医出版社
  • 主编:
  • 地址:北京市100036信箱188分箱
  • 邮编:100036
  • 邮箱:mjcpla@pmmp.com.cn
  • 电话:010-51927306
  • 国际标准刊号:ISSN:0577-7402
  • 国内统一刊号:ISSN:11-1056/R
  • 邮发代号:2-74
  • 获奖情况:
  • 全军医学期刊质量评比优秀期刊奖,北京市全优期刊奖,中国科学引文数据库来源期刊
  • 国内外数据库收录:
  • 俄罗斯文摘杂志,美国化学文摘(网络版),波兰哥白尼索引,荷兰文摘与引文数据库,荷兰医学文摘,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),瑞典开放获取期刊指南,中国北大核心期刊(2000版)
  • 被引量:30614