三-(2,3-二溴丙基)异氰脲酸酯通过线粒体信号通路致大鼠肝毒性的研究  

Hepatotoxicity of tri-(2,3-dibromopropyl)isocyanurate via mitochondrial signaling pathway in rats

作　　者：冯雅杰 綦峥[1] 杨明[1] 韩馥蕊 乐志威 孙源 FENG Ya-Jie;QI Zheng;YANG Ming;HAN Fu-Rui;LE Zhi-Wei;SUN Yuan(Engineering Research Center for Medicine,Harbin University of Commerce,Harbin Heilongjiang,150016,China)

机构地区：[1]药物工程技术研究中心,哈尔滨商业大学,黑龙江哈尔滨150076

出　　处：《毒理学杂志》2021年第2期146-151,158,共7页Journal of Toxicology

基　　金：中央支持地方高校改革发展基金优秀青年人才项目(2020YQ12);黑龙江省自然科学基金(LH2019D007);黑龙江省省属高等学校基本科研业务费科研(2020CX09)。

摘　　要：目的研究新型杂环类溴代阻燃剂三-(2,3-二溴丙基)异氰脲酸酯[Tri-(2,3-dibromopropyl)isocyanurate,TBC]对大鼠肝的毒性作用,并探讨TBC是否可通过线粒体途径诱导肝细胞凋亡。方法清洁级Wistar大鼠80只,随机分成4个剂量组(0、0.313、0.625和1.250)g/(kg·bw),每组雌雄各半,经口连续染毒28 d。通过血液学、血液生化指标及肝病理检查-检查探讨TBC对大鼠的肝毒性作用。采用Western blot法对TBC诱导线粒体凋亡通路的Bax、Bcl-xl、Bcl-2、Cytochrome C(Cyt-C)、Caspase-3和Caspase-9相关蛋白表达进行检测。结果与对照组比较,雌大鼠的红细胞计数、血红蛋白浓度、白细胞计数和淋巴细胞百分率随染毒剂量的增加而下降,与对照组比较,差异有统计学意义;雌、雄大鼠的天冬氨酸转氨酶和血清总蛋白随染毒剂量增加而升高,与对照组比较,差异有统计学意义。肝病理学检查显示随着染毒剂量的增大,大鼠的肝逐渐出现损伤,组织变性,甚至局部坏死。肝组织中Bcl-xl和Bcl-2蛋白随着染毒剂量的增高而下降,Bax、Cyt-C、Caspase-3、Caspase-9蛋白随着染毒剂量的增高而上升,呈现剂量-效应关系。结论TBC具有肝毒性,且可能与通过线粒体信号通路诱导细胞凋亡有关。Objective To investigate whether new heterocyclic brominated flame retardant tri-(2,3-dibromopropyl)isocyanurate(TBC)induced hepatotoxicity in rats via mitochondrial pathway.Methods 80 Wistar rats(weight:60~80 g)were randomly divided into four exposure groups(0、0.313、0.625、1.250)g/(kg·bw),half male rats and female rats in each group.All rats were orally administrated for 28 days.Blood routine,blood biochemical parameters and pathological examination of liver in rats.The expression of key proteins Bax、Bcl-xl、Bcl-2、Cytochrome C(Cyt-C)、Caspase-3、Caspase-9 were tested in TBC induced mitochondrial apoptosis pathway by western blot assay.Results The red blood cell count,hemoglobin concentration,white blood cell count and lymphocyte percentage of female rats were decreased with exposure dose.There was statistically significant compared with control group.Glutamic oxaloacetic transaminase,total protein of male and female rats increased with the increase of exposure dose,and there were significant differences compared with control group.The hepatic cell in rat appeared damage,tissue degeneration,even local necrosis as the dose increased under the pathological examination.The expression of protein Bcl-xl and Bcl-2 down regulated and the expression of protein Bax,Cytochrome C(Cyt-c),Caspase-3 and Caspase-9 protein up regulated with the increase of TBC dose.Conclusion TBC can induce hepatotoxicity in rats via mitochondrial pathway.

关 键 词：三-(2 3-二溴丙基)异氰脲酸酯 肝脏毒性 线粒体信号通路 

分 类 号：R994.3[医药卫生—毒理学] R114[医药卫生—药学]