乌司他丁对小鼠急性肺损伤保护作用及机制的研究

doi:10.3969/j.issn.1002-1949.2018.06.015

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摘要目的研究乌司他丁（ulinastatin, UTI）对急性肺损伤（acute lung injury，ALI）小鼠的保护作用，并探讨其机制。方法雄性SPF级C57/BL小鼠64只，按随机数字表均分为:健康对照组(Sham组)、Sham+UTI 组、脂多糖组（LPS组）、LPS+UTI组。气管内滴注LPS建立ALI模型，Sham+UTI组和LPS+UTI组建模前30 min皮下注射UTI 10 000 U/kg。监测各组小鼠72 h生存率。建模后24 h取支气管肺泡灌洗液（BALF）和肺组织, 检测BALF中炎性细胞、中性粒细胞和巨噬细胞数；测定肺组织湿/干质量比（W/D）；观察肺组织病理学变化并计算肺损伤评分；测定肺组织中髓过氧化物酶（MPO）活性及丙二醛（MDA）含量；测定肺组织中肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）、IL-6、IL-2 mRNA水平，检测肺组织中TLR4/NF-κB表达情况。结果 LPS+UTI组小鼠生存率较LPS组明显升高，差异有统计学意义（P<0.05）；LPS+UTI组肺组织W/D、肺组织病理评分及肺组织中MPO活性和MDA含量较LPS组明显降低，TNF-α、IL-1、IL-6、IL-2 mRNA水平较LPS组明显降低，且TLR4/NF-κB mRNA表达水平较LPS组显著降低，差异均具有统计学意义（P<0.05或P<0.01）。结论 UTI可减轻LPS诱导的ALI小鼠肺组织的炎性反应，提高ALI小鼠生存率，这可能与UTI影响TLR4/NF-κB信号通路有关。

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	李雪宁
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关键词 ：乌司他丁（UTI), 小鼠, 脂多糖(LPS), 急性肺损伤(ALI), Toll样受体4(TLR4), NF-κB信号通路, 机制

基金资助:天津市应用基础与前沿技术研究计划项目（13JCYBJC37500）；睿 E（睿医）急诊医学研究专项基金项目（R2015026）；天普研究基金项目（UF201315）；天津医科大学总医院青年孵育基金项目（ZYYFY2015010）

通讯作者: 柴艳芬（1965-）, 女，主任医师，硕士生导师，E-mail: Chaiyanfen2012@126.com。

作者简介: 李雪宁（1992-），女，硕士，E-mail: 858895384@qq.com

引用本文:

李雪宁，曹超，寿松涛，王军，柴艳芬. 乌司他丁对小鼠急性肺损伤保护作用及机制的研究[J]. 中国急救医学, 2018, 38(6): 527-.
Li Xue-ning, Cao Chao, Shou Song-tao, Wang Jun, Chai Yan-fen. Protective effect of ulinastatin on acute lung injury and its mechanism in mice. Chinese Journal of Critical Care Medicine, 2018, 38(6): 527-.

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http://www.cnemergency.org.cn/CN/10.3969/j.issn.1002-1949.2018.06.015 或 http://www.cnemergency.org.cn/CN/Y2018/V38/I6/527

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