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

沙利度胺衍生物ZSN-12抗急性肺损伤作用及机制探讨（英文）

作　　者：高小力[1] 孟祥豹[2] 蒋益民[3] 李中军[2] 叶加[1] 

机构地区：[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

出　　处：《Journal of Chinese Pharmaceutical Sciences》2013年第5期435-440,共6页中国药学（英文版）

基　　金：Beijing Natural Science Foundation(Grant No.7122097)

摘　　要：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.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(10,5,1μmol/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：Thalidomide derivative ZSN-12 Acute lung injury ANTI-INFLAMMATION 

分 类 号：R96[医药卫生—药理学]