邻苯二甲酸二丁酯对巨噬细胞吞噬能力的影响研究

Studies on the effect of dibutyl phthalate on the phagocytosis of macrophages

目的:近期台湾地区食品及饮料中添加邻苯二甲酸酯类(塑化剂)的安全问题受到广泛关注,已有研究证实邻苯二甲酸酯类物质能影响人类生殖系统发育,但其对人体免疫系统影响尚不清楚。本文研究邻苯二甲酸二丁酯对巨噬细胞吞噬能力的影响,以期揭示其对人类健康的危害。方法:使用不同浓度邻苯二甲酸二丁酯体外处理小鼠腹腔巨噬细胞24小时,然后进行巨噬细胞对细菌E.coli以及诱导凋亡的小鼠胸腺细胞的吞噬实验,并检测其吞噬率和吞噬指数,从而评价其对巨噬细胞吞噬能力的影响。用流式细胞仪检测邻苯二甲酸二丁酯对巨噬细胞表面吞噬相关分子CD11b、CD54、CD36、TLR4和CD64的影响;利用siRNA技术对吞噬相关受体CD36进行表达干扰,验证其在邻苯二甲酸二丁酯抑制巨噬细胞吞噬能力中的作用。结果:经过24小时体外处理,不同浓度邻苯二甲酸二丁酯对巨噬细胞吞噬能力均有抑制作用,并且具有剂量依赖性。此外,邻苯二甲酸二丁酯能显著降低巨噬细胞清道夫受体CD36的表达。结论:研究结果证实邻苯二甲酸二丁酯通过降低细胞膜表面CD36表达从而抑制巨噬细胞吞噬能力。

Objective：It has caused serious concern about phthalates,called ＇plasticizers＇,being added to certain foods and benerages manufactured in Taiwan.There have been several studies suggest that phthalate compounds have caused reproductive systems abnormalities of animals,but the association between immune system and phthalate esters is unknown.The effect of dibutyl phthalate on the phagocytosis of macrophages was studied to evalulate the potentially hazardous to humans.Methods：The phagocytosis of macrophage was analyzed after treated with different dose of dibutyl phthalate for 24 hours.Furthermore,phagocytosis associated molecules,such as CD11b,CD54,CD36,TLR4 and CD64,on the surface of macrophages were detected with flow-cytometry.To determine the role of CD36,a part of scavenger receptor,in the inhibitory effect of dibutyl phthalate on the phagocytosis of macrophages,CD36 was knock-down in macrophage with siRNA.Results：The phagocytosis of mouse peritoneal macrophage on E.coli and mouse apoptosic thymocyte cells was repressed after treatment with dibutyl phthalate for 24 hours and it showed dose dependent manner.Furthermore,the expression of CD36 on the macrophages was repressed by dibutyl phthalate.Conclusion：CD36 is a key factor which play a role in the effect of dibutyl phthalate on phagocytosis of macrophages.