沙利度胺衍生物ZSN-12抗急性肺损伤作用及机制探讨

doi:10.5246/jcps.2013.05.064

沙利度胺衍生物ZSN-12抗急性肺损伤作用及机制探讨

高小力, 孟祥豹, 蒋益民, 李中军^*, 叶加^*

1. 北京大学医学部药学院分子与细胞药理系, 北京 100191
2. 北京大学医学部药学院化学生物学系, 北京 100191
3. 北京大学医学部药学院医药卫生分析中心, 北京 100191

收稿日期:2013-04-25 修回日期:2013-05-07 出版日期:2013-09-15 发布日期:2013-09-15
通讯作者: 李中军*, 叶加*

The protective effects of thalidomide derivative ZSN-12 on acute lung injury

Xiaoli Gao, Xiangbao Meng, Yimin Jiang, Zhongjun Li^*, Jia Ye^*

1. Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
3. Department of Medical and Healthy Analysis Center, Peking University Health Science Center, Beijing 100191, China

Received:2013-04-25 Revised:2013-05-07 Online:2013-09-15 Published:2013-09-15
Contact: Zhongjun Li*, Jia Ye*

摘要/Abstract

摘要： 对沙利度胺衍生物ZSN-12的抗急性肺损伤作用及机制进行了研究。结果显示ZSN-12 (200 mg/kg) 明显改善油酸致小鼠急性肺损伤的病理改变; 抑制肺泡灌洗液(BALF)中中性粒细胞(PMN)的渗出和NO的大量释放(P<0.01, P<0.05), 抑制率分别为48%和33%。ZSN-12 (200, 100, 50 mg/kg)明显抑制二甲苯引起的鼠耳肿胀和角叉菜胶引起的足趾肿胀(P<0.01), 并呈剂量依赖, 给药3小时的抑制率分别为62%, 43%, 30%和60%, 47%, 33%; ZSN-12 (10, 5, 1 μmol/L)明显抑制ConA诱导的脾T细胞增殖(P<0.01), 抑制率分别为33%, 30%, 22%。综上所述, 沙利度胺衍生物ZSN-12对油酸型急性肺损伤有一定的保护作用, 其机制主要与其抗炎作用, 抑制中性粒细胞渗出, 减少NO释放, 抑制T细胞增殖有关。

关键词: 沙利度胺衍生物ZSN-12, 急性肺损伤, 抗炎

Abstract: The aim of this study was to evaluate the protective effect of thalidomide derivative ZSN-12 on acute lung injury induced by oleic acid in mice, and to investigate the possible mechanisms. The results showed that ZSN-12 (200 mg/kg) markedly improved the pathological changes of acute lung injury. The proportion of polymorphonuclear neutrophils (PMN) was reduced by 48% (P<0.01) and the content of nitric oxide (NO) in bronchoalveolar lavage fluid (BALF) was decreased by 33% (P<0.05). ZSN-12 produced significant anti-inflammatory effects in the models of xylene induced ear edema and carrageenan induced paw edema, in which ZSN-12 inhibited ear edema and paw swelling in a dose-dependent manner. The inhibition rates by ZSN-12 dosed at 200, 100, 50 mg/kg were 62%, 43%, and 30% in ear edema, respectively and 60%, 47%, and 33% in paw edema, respectively, at 3 h. Meanwhile, ZSN-12 (10, 5, 1 μmol/L) significantly restrained the ConA-induced T lymphocyte proliferation, with the inhibition rates of 33%, 30% and 22%, respectively (P<0.01). In conclusion, the present study showed that administration of thalidomide derivative ZSN-12 exerted significant protective effect in acute lung injury induced by oleic acid in mice,which may be related to its anti-inflammation effect. ZSN-12 inhibited the effusion of PMN, reduced the release of NO, and suppressed the proliferation of T lymphocyte.

Key words: Thalidomide derivative ZSN-12, Acute lung injury, Anti-inflammation

中图分类号:

R962

Supporting: Foundation item: Beijing Natural Science Foundation (Grant No. 7122097).
^*Corresponding author. Tel.: 86-10-82802653; 86-10-82801714

高小力, 孟祥豹, 蒋益民, 李中军^*, 叶加^*. 沙利度胺衍生物ZSN-12抗急性肺损伤作用及机制探讨[J]. , DOI: 10.5246/jcps.2013.05.064.

Xiaoli Gao, Xiangbao Meng, Yimin Jiang, Zhongjun Li^*, Jia Ye^*. The protective effects of thalidomide derivative ZSN-12 on acute lung injury[J]. , DOI: 10.5246/jcps.2013.05.064.

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