三(1,3-二氯-2-丙基)磷酸酯诱发肝脏损害及病理改变研究Tris (1,3-dichloro-2-propyl) Phosphate Induced Hepatic Damages and Pathological Changes
李学彦;王思敏;周启星;邵晓东;张永国;胡献刚;
摘要(Abstract):
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)·d(-1)、250 mg·kg(-1)、250 mg·kg(-1)·d(-1)·d(-1)和500 mg·kg(-1)和500 mg·kg(-1)·d(-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。
关键词(KeyWords): 有机磷阻燃剂;TDCPP;大鼠;肝功损害;健康效应;病理改变
基金项目(Foundation): 国家自然科学基金面上项目(31670508)
作者(Authors): 李学彦;王思敏;周启星;邵晓东;张永国;胡献刚;
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