摘要：
本研究观测有机磷酯阻燃剂(OPFRs)污染是否可以诱发肝脏损害,考察其发生及发展程度,并探讨其发生机理,为有机磷阻燃剂污染的防治和相关疾病的有效治疗提供基础数据和科学依据.实验以大鼠为动物模型,将60只SPF级SD雄性大鼠分为5组,每组12只,选取典型的氯代有机磷阻燃剂三(1,3-二氯-2-丙基)磷酸酯(TDCPP)对大鼠进行染毒,空白对照组不做任何处理,溶剂对照组以相同体积的橄榄油灌胃,染毒组以不同剂量的TDCPP进行灌胃(125 mg·kg-1·d-1、250 mg·kg-1·d-1和500 mg·kg-1·d-1),每周测量体重,于第4周和第8周取血检测肝功及其他生化指标,在第8周每组抽取3只大鼠取肝脏组织做HE染色,并用透射电镜观察分析肝组织病理学改变.TDCPP对大鼠染毒8周后,结果表明:(1)体重指标在灌胃1周后开始发生差异,TDCPP处理组大鼠的体重有下降的趋势,染毒组与空白对照组和溶剂对照组相比较,差异显著(*P＜0.05,**P＜0.01),其中高剂量灌胃组的体重下降最为明显(**P＜0.01);(2)血清肝功指标表现出显著变化,血清谷丙转氨酶、谷草转氨酶、胆固醇和甘油三脂水平在第8周呈现明显下降趋势,染毒组与空白对照组和溶剂对照组比较,差异明显(*P＜0.05,**P＜0.01);(3)TDCPP暴露组生理生化指标变化明显,血清乙酰胆碱酯酶活性显著降低,MDA含量显著升高,SOD活力显著性降低,造成氧化损伤,与空白对照组和溶剂对照组比较,差异显著(*P＜0.05,**P＜0.01);(4)病理切片结果显示染毒组与对照组比较,细胞坏死现象明显,且高剂量组坏死更为严重.研究结果显示:TDCPP可引起大鼠体重明显下降,大鼠肝脏细胞损伤、合成功能下降,造成肝脏代谢功能紊乱,造成较为严重的肝损伤.%In order to provide basic data and scientific basis for the prevention of organic phosphorus flame retardants (OPFRs) pollution and effective treatment of related diseases, whether OPFRs could induce liver damages and their occurrence and degree of development were investigated, and the related mechanisms were explored. Rats were used as the animal model in this experiment. The male Sprague-Dawley rats were divided into 5 groups, and there were 12 rats in each group. The rats were exposed to tris (1, 3-dichloro-2-propyl) phosphate (TDCPP), a typical chlorophosphorus flame retardant. The control group received no treatment, the solvent group was given with the same volume of olive oil, and the exposure group was given with TDCPP in different doses (125 mg·kg-1·d-1, 250 mg·kg-1·d-1 and 500 mg·kg-1·d-1) by stomach. The body weight was measured every week and the biochemical indexes of liver function in serum were measured at the end of the 4 th and 8 th week. At the end of 8 th week, 3 rats from each group were sacrificed to obtain the liver for the hematoxylin-eosin staining and analysing histopathological changes using the transmission electron microscope. After rats were exposed to TDCPP for 8 weeks, the body weight of TDCPP-treated rats had a decreasing tendency. There were some differences in body weight after TDCPP administration for 1 week. Compared with the control group and the solvent group, the body weight of rats in TDCPP-treated group decreased significantly (*P ＜0.05, **P ＜0.01), and the loss of weight was more obvious in high-dose group (**P＜0.01). Liver function indicators in serum showed abnormalities, alanine aminotransferase, aspartate aminotransferase, cholesterol and triglyceride levels of rats in TDCPP-treated group had a significant downward trend, compared with the control group and the solvent group (*P＜0.05, **P＜0.01). The activity of serum acetylcholinesterase in TDCPP-treated group decreased significantly, compared with the control group and the solvent group (*P＜0.05, **P＜0.01). After exposed to TDCPP, the levels of MDA increased significantly and the activity of SOD decreased significantly (*P＜0.05, **P＜0.01), thus resulting the oxidative damage in livers. The pathological section results showed that the liver cells of rats exposed to TDCPP were injured, and the necrosis was more severe in the high-dose group. The results showed that TDCPP could cause the loss of body weight of rats significantly, TDCPP also caused liver cell damages and perturbed the synthesis function of liver, thus resulting the dysfunction in liver metabolism and severe hepatic damages.
