邻苯二甲酸二异壬酯单独暴露及与褪黑素联合作用对小鼠脑组织损伤研究

Effects of diisolonyl phthalate alone and combined with melatonin on brain injury in mice

人类神经系统成熟的海马神经元细胞不能进行复制与自我修复,导致了神经系统易受到环境污染物损伤的风险.邻苯二甲酸二异壬酯(Diisonyl phthalate,DINP)是一种增塑剂替代产品,类雌激素作用较弱,正受到欧盟的推广使用.虽然目前已有一些研究表明了DINP的毒性,但有关其神经毒性的体内研究国内还较少.因此,本研究探讨了DINP单独暴露及与褪黑素联合作用对小鼠脑组织的影响.行为学分析显示,经灌胃200 mg·kg^(-1)·d^(-1)的DINP会导致小鼠行为学出现明显变化;脑组织病理学观察、免疫组化分析(半胱氨酸蛋白酶3(Caspase-3)、胶质纤维酸性蛋白(GFAP))、氧化应激水平检测(活性氧簇(ROS)、还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)活性、8-羟基脱氧鸟苷(8-OH-d G)、DNA-蛋白质交联(DPC))、炎症水平检测(肿瘤坏死因子ɑ(TNF-ɑ)、白介素1β(IL-1β))结果显示,小鼠脑组织海马区出现了病理学损伤,氧化应激和炎症水平上升(p<0.01).DINP处理后予以50 mg·kg-1·d-1的褪黑素可以降低氧化应激水平,对小鼠脑组织海马区起到保护作用.以上数据表明,实验剂量(200 mg·kg^(-1)·d^(-1))DINP处理后可以导致小鼠脑组织损伤,同时予以褪黑素可以在一定程度上缓解这种损伤.

Mature hippocampal neurons in the human nervous system are uncapable of regeneration and repairment,while the nervous system is susceptible to environmental contaminants. Diisonyl phthalate（ DINP） is a plasticizer substitute that is being promoted by the European Union for its weak estrogen-like effects. Meanwhile DINP was shown that had neurotoxicity in a few domestic researches. The purpose of this study is to investigate the effects of DINP with or without melatonin on brain injury in mice. Behavioral analysis showed that 200 mg·kg-1·d-1 DINP by oral administration significant changed the behaviour of mice. Histopathological observation,immunohistochemically analysis（ Caspase-3,GFAP）,detection of oxidative stress levels（ROS,GSH,SOD,8-OH-d G,DPC）,and the levels of inflammatory（TNF-ɑ,IL-1β） showed that the hippocampus of brain tissue of the mice appeared pathological damage,oxidative stress and inflammation levels increased（ p0.01）. The combination of 50 mg·kg-1·d-1 melatonin could reduce oxidative stress induced by DINP and protect the hippocampus of brain tissue in mice. These data suggest that exposure to high doses of DINP（ 200 mg·kg-1·d-1）cause brain damage in mice,but melatonin protects the brain from this damage induced by DINP.