1、4期Aryl Hydrocarbon Receptor-mediated Cardiac Toxicity in Adult ZebrafishInduced by Tetrabromobisphenol ASHAN Jing1,2,MA Xiaofa1,2,WU Mengyu1,2,LIN Yujia1,2,WANG Yi1,2,WANG Rui1,2,XU Haiming1,2(1.School of Public Health and Management,Ningxia Medical University,Yinchuan750004,China;2.TheKey Laborator
2、y of Environmental Factors and Chronic Disease Control of Ningxia,Yinchuan750004,China)Abstract:ObjectiveIn this study,zebrafish(Danio rerio),a model organism,was used as an experimentalanimal,and CH223191(CH),an aromatic hydrocarbon receptor(AhR)inhibitor,was used to explore the role ofAhR in the c
3、ardiac toxic effect of tetrabromobisphenol A(TBBPA)on zebrafish.MethodsAdult zebrafish wererandomly divided into six groups for exposure,namely solvent control group(DMSO),CH group(0.05 mol L-1),TBBPA exposure groups(10,100,1 000 nmol L-1),and CH+TBBPA(1 000 nmol L-1)group.After 30 days ofexposure,t
4、he body weight and body length were measured.The expression of AhR-related genes(ahr2,cyp1a1and cyp1a2),cardiac function-related genes(sox9b,nkx2.5,gate4,myh6,tbx5 and vmhc)and reactive oxygenspecies-related genes(nrf2,gpx1a,sod1,sod2 and cat)in cardiac tissue were detected by qRT-PCR.Theantioxidant
5、 enzymes(SOD,CAT and GSH-Px/GPX)activities in liver tissue were tested by commercial kits.ResultsCompared with the DMSO control group,there was no significant difference in body weight and bodylength in all exposure groups(P all0.05).The results of qRT-PCR showed that AhR-related genes(ahr2,cyp1a1 a
6、nd cyp1a2)was down-regulated in the CH group,while up-regulated in 10,100,1 000 nmol L-1TBBPA groups(P all0.05).Compared with the 1 000 nmolL-1TBBPA exposure group,these AhR relatedgenes were decreased to a certain extent in the CH+1 000 nmolL-1TBBPA group(P all0.05).The cardiacfunction-related gene
7、s(sox9b,nkx2.5,gate4,myh6,tbx5 and vmhc)were down-regulated in the 1 000 nmol L-1TBBPA group(P all0.05).The reactive oxygen species-related genes(gpx1a,sod1,sod2 and cat)weredown-regulated while nrf2 was up-regulated in the 1 000 nmol L-1TBBPA group(P all0.05).The results of theantioxidant enzyme ac
8、tivities showed that hepatic SOD,CAT and GSH-Px/GPX activities were decreased in the1 000 nmol L-1TBBPA group(P all0.05).Specifically,the activities of these enzymes were equivalent to 0.45times,0.57 times and 0.44 times of the DMSO control group respectively.Compared with the 1 000 nmol L-1TBBPA gr
9、oup,SOD,CAT and GSH-Px/GPX activities were increased to a certain extent in the CH+1 000 nmol L-1TBBPA group(P all0.05).ConclusionThe exposure of TBBPA at environmentally relevantconcentrations can cause oxidative damage and affect the expression levels of key genes of cardiac function byactivating
10、the AhR signaling pathway,which ultimately leads to cardiac toxicity.Key words:tetrabromobisphenol A;aryl hydrocarbon receptor;zebrafish;cardiac toxicity;oxidative stress单婧,等.芳香烃受体介导四溴双酚A致斑马鱼成鱼心脏毒性作用有的作者将离心机转速用 rpm 表示,这是非法定单位的写法。正确的写法是:当低速离心时用 r min-1表示;当高速或超速离心时用相对离心力“g”表示,g 是斜体,前面是乘号。(本刊编辑部)离心机转速的写法及相对离心力的正确表示331