饮水中二溴乙酸对小鼠免疫功能影响机制的研究

Study on the mechanism of immune dysfunction induced by dibromoacetic acid in drinking water in mice

目的探讨二溴乙酸对小鼠免疫功能影响的机制。方法清洁级BALB／c小鼠40只，分为四组：即二溴乙酸5、20和50mg／kg剂量组以及阴性对照。连续灌胃28d后，检测脾和胸腺细胞因子白细胞介素（IL）-2、IL-4分泌水平，脾和胸腺内细胞凋亡率，以及凋亡相关基因（Fas，Bcl-2，TRAF-2和bax）和蛋白（Fas／FasL）的表达。结果与阴性对照组相比，二溴乙酸染毒组脾细胞的IL-2分泌水平明显增加（P〈0．01）而胸腺细胞的IL-2分泌水平降低（50mg／kg剂量组有统计学意义，P〈0．05），脾细胞和胸腺细胞的IL4的分泌水平明显降低（P〈0．01）。脾和胸腺细胞凋亡率明显增加。胸腺和脾内的Fas和TRAF2基因表达显著增加，Fas／FasL的蛋白表达显著增加，具有统计学意义（P均为〈0．05）。结论饮水中二溴乙酸对小鼠免疫器官的损伤是通过Fas／FasL途径诱导细胞凋亡。

Objective To investigate the mechanism of immune function alteration induced by dibromoacetic acid（DBA） in mice. Methods： 40 SPF（specific-pathogen-free） BALB/c mice were divided into four groups （ control, DBA 5 mg/kg, 20 mg/kg and 50 mg/kg）. After intragastric administration for 28 days ,the cytokine IL-2 and IL-4 secretion, the percentage of cell apoptosis and apoptosis related gene （ Fas, Bcl-2, TRAF- 2 and bax） and protein （Fas/FasL） expression in the spleen and thymus were detected. Results DBA significantly increased the level of IL-2 in the spleen（ P 〈 0. 01 ） but decreased in the thymus（ P 〈 0. 05 ）. The level of IL-4 secretion significantly decreased IL-2 in the spleen and thymus. The percentage of apoptosis increased in a dose-dependent manner after DBA exposure. The expression of Fas and TRAF2 genes increased significantly in thymus and spleen（ P 〈 0. 05）. The expression of Fas/FasL proteins were increased significantly in thymus and spleen（ P 〈 0. 05 ）. Conclusion DBA changes the cytokine level in the thymus and spleen. The immunecell apoptosis mediated by the Fas/FasL pathway may be the potential mechanism underlying this immunotoxicity.