天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (9): 985-988.doi: 10.11958/j.issn.0253-9896.2015.09.007

• 实验研究 • 上一篇    下一篇

乌司他丁联合异甘草酸镁对肺纤维化大鼠肺组织TGF-β1和CTGF表达的影响

刘伟伟1,聂卫1,袁玲2,郑洪2,崔晓雪1,沈洪昇1,刘大卫1   

  1. 1天津市医药科学研究所 （邮编300020）； 2天津市第一中心医院
  • 收稿日期:2015-03-26 修回日期:2015-04-17 出版日期:2015-09-15 发布日期:2015-09-15
  • 通讯作者: 刘伟伟 E-mail:534833136@qq.com
  • 作者简介:王继权 （1989）， 男， 硕士在读， 主要从事脊髓损伤的机制及修复研究
  • 基金资助:
     国家自然科学基金资助项目 （81272074）； 辽宁省高等学校优秀人才支持计划项目 （LJQ2014091）； 辽宁医学院校长基金项目 M2014011）

Effects of combination of ulinastatin and magnesium isoglycyrrhizinate on expression of TGF-β1 and CTGF in lung tissue of rats with pulmonary fibrosis

LIU Weiwei 1 , NIE Wei 1 , YUAN Ling1 , ZHENG Hong2 , CUI Xiaoxue1 , SHEN Hongsheng1 , LIU Dawei 1   

  1. 1 Tianjin Institute of Medical and Pharmaceutical Sciences, Tianjin 300020, China ;2 Tianjin First Center Hospital
  • Received:2015-03-26 Revised:2015-04-17 Published:2015-09-15 Online:2015-09-15

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摘要： 摘要： 目的 观察乌司他丁联合异甘草酸镁对博莱霉素 （BLM） 诱导的肺纤维化大鼠肺组织转化生长因子β1 （TGF-β1） 和结缔组织生长因子 （CTGF） 表达的影响。方法 90 只大鼠随机分为以下 5 组： BLM 组、 甲泼尼龙琥珀酸钠 （MTH） 组、 乌司他丁 （UTI） 组、 异甘草酸镁 （MgIG） 组、 乌司他丁联合异甘草酸镁 （UTI+MgIG） 组， 各 18 只。5 组均以气管内注入 BLM 建立大鼠肺纤维化模型， 造模成功 24 h 后， BLM 组大鼠每日腹腔注射生理盐水， 其余各组给予相应药物腹腔注射。每组分别于第 7、 14 和 28 天处死 6 只， HE 染色评价肺组织肺泡炎及纤维化程度， 免疫组化测定肺组织 TGF-β1 和 CTGF 的表达水平。结果 （1） 药物干预各组肺泡炎及肺纤维化程度均较 BLM 组有所减轻， 其中 UTI+MgIG 组第 7、 14 天肺泡炎程度， 第 14、 28 天肺纤维化程度与 BLM 组差异有统计学意义 （P < 0.05）。（2） 药物干预各组TGF-β1和CTGF 的表达水平在各时间点均较同期BLM 组有所降低； UTI+MgIG 组TGF-β1的表达水平在第7、 14天时明显低于UTI组和MgIG组， 第28天时明显低于MTH组、 UTI组和MgIG组 （P < 0.05）； UTI+MgIG组CTGF的表达水平在第 7 天时明显低于 UTI 组和 MgIG 组， 第 14、 28 天时明显低于 MTH 组、 UTI 组和 MgIG 组 （P < 0.05）。结论 UTI联合MgIG能减轻BLM诱导的大鼠肺泡炎及纤维化程度， 其机制可能与下调TGF-β1和CTGF的表达有关。

关键词: 肺纤维化, 转化生长因子β1, 大鼠, Wistar, 结缔组织生长因子, 乌司他丁, 异甘草酸镁

Abstract: Objective To investigate the effects of ulinastatin (UTI) combined with magnesium isoglycyrrhizinate (MgIG) on the expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in lung tis⁃ sue of rats with pulmonary fibrosis induced by bleomycin (BLM). Methods Ninety Wistar rats were randomly divided into five groups: BLM group, methylprednisolone (MTH) group, UTI group, MgIG group and UTI combined with MgIG (UTI + MgIG) group, n=18 for each group. The rat model of pulmonary fibrosis was established by injecting bleomycin through tra⁃ chea in five groups. Twenty-four hours after treatment with BLM， rats were treated with normal saline every day in BLM group, and rats were treated by corresponding drugs in other groups. Six rats of each group were killed at the 7th,14th and 28th day respectively. The pathological changes of alveolitis and pulmonary fibrosis were evaluated by HE staining, and ex⁃ pression levels of TGF-β1 and CTGF in lung tissues were detected by immunohistochemistry method. Results (1) Com⁃ pared with BLM group, the degree of alveolitis and pulmonary fibrosis was reduced in other groups. There was significant dif⁃ ference in alveolitis at the 7th and 14th day between UTI + MgIG group and BLM group. And there was significant difference in pulmonary fibrosis at the 14th and 28th day between UTI + MgIG group and BLM group (P < 0.05). (2) Compared with BLM group, the expression levels of TGF-β1 and CTGF were decreased in other groups. In UTI + MgIG group, the expres⁃ sion levels of TGF-β1 were significantly lower at the 7th and 14th day compared with those in UTI group and MgIG group, and which were significantly lower at the 28th day than those in MTH group, UTI group and MgIG group (P < 0.05). The ex⁃ pression levels of CTGF were significantly lower at the 7th day in UTI + MgIG group than those in UTI group and MgIG group, and which were significantly lower at the 14th and 28th day than those in MTH group, UTI group and MgIG group (P < 0.05). Conclusion The combination of UTI and MgIG can alleviate alveolitis and fibrosis in BLM-induced pulmonary fibrosis rats, which might related with the down-regulation of TGF-β1 and CTGF expressions.

Key words: pulmonary fibrosis, transforming growth factor beta1, rats, Wistar, connective tissue growth factor, ulinastatin, magnesium isoglycyrrhizinate