孕早期双酚A暴露对仔鼠Th1/Th2、Treg/Th17及AhR/TLR4/NF-κB的影响  

Effects of bisphenol A exposure in early pregnancy on Th1/Th2,Treg/Th17 and AhR/TLR4/NF-κB of offspring mice

作　　者：闫悦 冯娟 康智忠[3] 李龙 王晓娟[5] YAN Yue;FENG Juan;KANG Zhizhong;LI Long;WANG Xiaojuan(Anyang Vocational and Technical College,Zhengzhou University,Anyang 455000,China;Henan Huahui Inspection and Research Institute Co.Ltd.,Anyang 455000,China;Anyang Center for Disease Control and Prevention,455000;Public Security Bureau of Anyang,Anyang 455000,China;Department of Medicine,Anyang Hospital of Traditional Chinese Medicine,Anyang 455000,China)

机构地区：[1]郑州大学安阳职业技术学院,455000 [2]河南华惠检测研究院有限公司,安阳455000 [3]安阳市疾病预防控制中心,455000 [4]安阳市公安局,455000 [5]安阳市中医院内科,455000

出　　处：《免疫学杂志》2021年第12期1071-1076,共6页Immunological Journal

基　　金：国家自然科学基金项目(81773404)。

摘　　要：目的探讨孕早期双酚A(BPA)暴露对仔鼠Th1/Th2和Treg/Th17及AhR/TLR4/NF-κB的影响。方法购置C57BL/6小鼠,雌鼠和雄鼠按照2:1比例合笼交配后,将确认怀孕雌鼠随机分为对照组、低剂量组、中剂量组和高剂量组,实验组自妊娠第0天至第18天分别以8、40和200 mg/kg的BPA溶液(以壬基酚进行标记)灌胃,对照组以等量玉米油灌胃。子代出生21 d后断乳,每窝随机选取1只仔鼠进行下一步研究。比较4组仔鼠体质量、脾质量和脾脏指数,脾脏Th1、Th2、Treg及Th17细胞水平,脾脏AhR/TLR4/NF-κB信号通路蛋白表达水平。结果断乳时,与对照组比较,低剂量组仔鼠脾质量和脾脏指数显著增加(P<0.05);中剂量组仔鼠脾脏指数显著增加(P<0.05);高剂量组仔鼠体质量和脾质量显著降低(P<0.05);低剂量组、中剂量组仔鼠脾脏Th1细胞比例显著降低,Th2细胞比例显著升高(P<0.05);各BPA剂量组仔鼠脾脏Th1/Th2比值显著降低(P<0.05)。中剂量组和高剂量组仔鼠Th17细胞比例显著升高(P<0.05),Treg/Th17比值显著降低(P<0.05);各BPA剂量组仔鼠脾脏AhR、TLR4和NF-κB蛋白表达水平显著升高(P<0.05)。结论孕早期BPA暴露可通过激活AhR/TLR4/NF-κB信号通路造成仔鼠Th1/Th2失衡及Treg和Th17细胞分化异常。This study aimed to investigate the effects of bisphenol A(BPA)exposure in early pregnancy on Th1/Th2,Treg/Th17 and AhR/TLR4/NF-κB of offspring mice.C57 BL/6 female mice were mated with male mice at ratio 2:1,then the pregnant mice were randomly divided into four groups:control group,low-dose group,mediumdose group and high-dose group.The three experimental groups were given 8,40 and 200 mg/kg BPA solution by gavage from day 0 to day 18 of pregnancy,while control group was given the same amount of corn oil.The offspring were weaned at 21 d after birth,and one litter rat was randomly selected from each group for further study.Then various indexes were compared among groups,including body weight,spleen weight,spleen index,spleen Th1,Th2,Treg and Th17 cell levels,and spleen AhR/TLR4/NF-κB signaling pathway proteins expression levels.Data showed a significant increase in spleen weight and spleen index in the low-dose group,as compared to the control group at weaning(P<0.05),and the spleen index of offspring mice in medium-dose group was significantly increased(P<0.05),meantime,the weight and spleen weight of offspring mice in high-dose group were significantly reduced(P<0.05).The proportion of Th1 cells in the spleen of offspring mice of the low-dose group and mediumdose group was significantly decreased(P<0.05),while the proportion of Th2 cells increased significantly(P<0.05);the proportion of Thl/Th2 in spleen of offspring mice of each BPA treatment group was significantly decreased(P<0.05).The proportion of Th17 cells in spleen of offspring of medium-dose group and high-dose group were significantly increased(P<0.05),while the ratio of Treg/Th17 was significantly reduced(P<0.05);the protein expression levels of AhR,TLR4 and NF-κB in offspring of each BPA treatment group were significantly increased(P<0.05).To sum up,BPA exposure during the first trimester of pregnancy may cause Thl/Th2 imbalance and abnormal differentiation of Treg and Th17 cells by activating AhR/TLR4/NF-κB signaling pathway.

关 键 词：双酚A TH1/TH2 Treg/Th17 AhR/TLR4/NF-κB信号通路 

分 类 号：R714[医药卫生—妇产科学]