沙利度胺对油酸诱发小鼠急性肺损伤的保护作用

The protective effects of thalidomide on acute mice lung injury induced by oleic acid

目的:观察沙利度胺对油酸诱发小鼠急性肺损伤的保护作用,并初步探讨其可能的作用机制。方法:将实验动物随机分为5组:正常组、模型组、地塞米松阳性对照组(Dex,10mg·kg^(-1),ig)、沙利度胺低、高剂量组(Tha,50,100mg·kg^(-1),ig)。利用油酸诱发小鼠急性肺损伤,光镜下观察肺组织病理学变化,测定支气管肺泡灌洗液(BALF)中蛋白质及前列腺素E_2(PGE_2)含量。结果:与模型组比较,Tha组均使渗出性病变及粒细胞浸润明显改善,低剂量组减少BALF中蛋白含量,抑制率为28.9%(P<0.01);高剂量组降低肺系数及BALF中蛋白与PGE_2含量,抑制率分别为27.8%,32.2%,21.9%(P<0.01);但两剂量组对小鼠体重、脾及胸腺重量指数均无影响。结论:沙利度胺对油酸诱发的小鼠急性肺损伤有一定保护作用;抑制PGE_2生成是其作用机制之一。

Objective: To explore effects and mechanism of thalidomide in the prevention of acute lung injury (ALI) induced by oleic acid in mice. Methods: The experimental mice were randomly allocated to one of five groups: normal, model, dexamethasone (10mg·kg^(-1), ig) as positive control, low and high dosing of thalidomide (50 and 100mg·kg^(-1), ig). The ALI model was set up by intravenous injection of oleic acid. The lung histopathologic examination was conducted under light microscopy. The protein and PGE_2 in bronchoalveolar lavage fluid (BALF) were quantified. Results: Acute exudative inflammation and neutrophil leukocyte infiltration were significantly reduced in both thalidomide groups. Compared with the model group, the quantity of protein in BALF was greatly reduced to 28.9% in the low dosing group of thalidomide (P<0.01). The lung weight index and the quantities of protein and PGE_2 in BALF were markedly decreased to 27.8%, 32.2%, 21.9%, respectively, in the high dosing group of thalidomide (P<0.01). No statistical difference in the body weight, the weight index of spleen and thymus gland was observed in both dosing group of thalidomide. Conclusion: Thalidomide protects the acute mice lung injury induced by oleic acid by inhibiting PGE_2.