塑化剂DEHP暴露对小鼠巨噬细胞的免疫毒性作用

Immunotoxicity of di(2-ethylhexyl)phthalate to macrophages

为了研究邻苯二甲酸二乙基己酯(DEHP)对巨噬细胞的免疫毒性,采用不同浓度剂量DEHP处理小鼠巨噬细胞株RAW264.7细胞和腹腔巨噬细胞,通过检测细胞吞噬、细胞因子分泌及活性氧水平变化探讨DEHP暴露对免疫系统的毒性作用。结果表明:高浓度(20、40、80 mg·L-1)DEHP处理48 h后对RAW264.7细胞可造成急性损伤。低浓度(1、5、10 mg·L-1)DEHP连续染毒处理10代后,RAW264.7细胞吞噬红细胞百分率及吞噬指数显著抑制(P<0.05)。RAW264.7细胞分泌TNF-α、IL-12和IL-23等细胞因子能力明显降低,并表现出一定的剂量-效应关系。随着DEHP暴露浓度的增加,DEHP染毒造成RAW264.7细胞内活性氧产生,受损加剧。除此之外,DEHP暴露还能明显抑制小鼠腹腔巨噬细胞对红细胞的吞噬能力(P<0.05)。以上结果表明,DEHP暴露对巨噬细胞具有免疫抑制作用,损伤了巨噬细胞正常免疫功能发挥。

To evaluate the potential immunotoxicity of di （2-ethylhexyl） phthalate （DEHP）, RAW264.7 cells and peritoneal macrophages were treated with different concentrations of DEHP. Further, the phagoeytosis efficiency and eytokine secretion and reactive oxygen species （ ROS ） production ability of RAW264.7 cells, and adherence ability and phagoeytosis efficiency of peritoneal maerophages were determined. The results revealed that the phagocytosis efficiency of RAW264.7 cells treated with 1, 5 mg·L^-1 and 10 mg·L^-1 DEHP was significantly inhibited. The concentration of tumor necrosis faetor（TNF）-α, interleukin（IL）-12, and IL-23 decreased significantly in the cell culture supernatant. Furthermore, there was a dose-effect relationship between DEHP exposure and concentration of TNF-α, IL-12, and IL-23. The production of ROS in DEHP-treated RAW264.7 cells was inhibited significantly with increase in the concentration of DEHP. Further, DEHP inhibited the adhesion ability and phagocytosis efficiency of peritoneal maerophages collected form DEHP-treated mice. These results indicate that DEHP treatment can inhibit the normal function of both RAW264.7 cells and peritoneal maerophages.