重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对脂多糖致大鼠急性肺损伤的保护作用

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (2): 140-143.

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对脂多糖致大鼠急性肺损伤的保护作用

王世婷, 郭竹英, 徐芒华, 矫强, 高丰厚

上海交通大学医学院附属第三人民医院实验中心, 上海201900

收稿日期:2008-07-23 修回日期:2009-01-24 出版日期:2009-02-26 发布日期:2020-10-30
通讯作者: 郭竹英, 女, 硕士, 副主任医师, 研究方向:多脏器急性损伤的实验研究。Tel:021-56691101-6943 　E-mail:zyguoo@126.com
作者简介:王世婷, 女, 硕士, 检验师。Tel:021-56691101-6944 　E-mail:wswsting@163.com

Protectve effects of recombinant human tumor necrosis factor receptor: Fc fusion protein on acute lung injury induced by lipopolysaccharide in rats

WANG Shi-ting, GUO Zhu-ying, XU Mang-hua, JIAO Qiang, GAO Feng-hou

Experimental Center, School of Medicine the No.3 People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 201900, China

Received:2008-07-23 Revised:2009-01-24 Online:2009-02-26 Published:2020-10-30

摘要/Abstract

摘要： 目的:探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR :Fc)对脂多糖(LPS)致大鼠急性肺损伤的保护作用及其机制。方法:建立大鼠急性肺损伤模型, 随机分为对照组、rhTNFR:Fc 组、LPS 组和rhTNFR :Fc +LPS 组。给药后记录各组大鼠死亡情况, 测定肺组织湿重干重比,HE染色观察肺组织病理学改变, 检测血清TNF-α含量及其生物活性。结果:LPS 注射后大鼠死亡率及肺湿重干重比显著高于对照组(P <0.05),HE染色可见大鼠肺间质充血、水肿, 大量炎性细胞浸润, 血清TNF-α含量及生物活性增高;rhTNFR :Fc+LPS 组大鼠死亡率降低, 肺组织病理损伤明显减轻, 血清TNF-α生物活性显著低于LPS 组(P <0.05)。结论:rhTNFR:Fc 通过中和TNF-α, 降低TNF-α生物活性, 有效减轻LPS 引起的大鼠急性肺损伤。

关键词: 脂多糖, 急性肺损伤, 肿瘤坏死因子-α, rhTNFR:Fc

Abstract: AIM: To investigate the mechanisms and protective effects of recombinant human tumor necrosis factor receptor :Fc fusion protein (rhTNFR:Fc) on the acute lung injury induced by lipopo1ysaccharide (LPS)in rats.METHODS: The rat model of acute lung injury was established with LPS and the rats were randomly divided into four groups :control group, rhTNFR: Fc group, LPS group and rhTNFR:Fc +LPS group.After administration, the rats'death was recorded, the pulmonary wet dry weight ratios were determined, the changes of lung histopathology were observed by HE dyeing, the levels of TNF-αand the bioactivity in serumwere detected.RESULTS: Compared with control group the rats'mortality rate and pulmonary wet dry weight ratio were significantly higher in the LPS group (P <0.05).The pathological examination showed lung interstitial hyperemia, oedema, and generous inflammatory cell infiltrate.The levels of TNF-αand the bioactivity in serum increased significantly (P <0.05).The mortality rate decreased and the lung pathology injury obviously ameliorated in rhTNFR :Fc +LPS group.The TNF-αbioactivity in serum decreased significantly (P <0.05)compared with the LPS group.CONCLUSION: rhTNFR :Fc could degrade TNF-αbioactivity and abate the acute lung injury induced by LPS in rats by binding TNF-α.

Key words: lipopolysaccharide, acute lung injury, TNF-α, protection effects of rhTNFR:Fc

中图分类号:

R965.2

王世婷, 郭竹英, 徐芒华, 矫强, 高丰厚. 重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对脂多糖致大鼠急性肺损伤的保护作用[J]. 中国临床药理学与治疗学, 2009, 14(2): 140-143.

WANG Shi-ting, GUO Zhu-ying, XU Mang-hua, JIAO Qiang, GAO Feng-hou. Protectve effects of recombinant human tumor necrosis factor receptor: Fc fusion protein on acute lung injury induced by lipopolysaccharide in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(2): 140-143.

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