乳化剂吐温-80和丁酸对辐射诱导胆汁酸肠肝循环障碍的影响  

Effects of Tween-80 and butyric acid on radiation-induced bile acid enterohepatic circulation disturbance and the treatment strategy

作　　者：李源[1] 樊赛军[1] 肖惠文[1] 董佳丽[1] 张书琴 崔明[1] Li Yuan;Fan Saijun;Xiao Huiwen;Dong Jiali;Zhang Shuqin;Cui Ming(Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine,Institute of Radiation Medicine,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin 300192,China)

机构地区：[1]中国医学科学院北京协和医学院放射医学研究所天津市放射医学与分子核医学重点实验室,天津300192

出　　处：《中华放射医学与防护杂志》2021年第5期321-326,共6页Chinese Journal of Radiological Medicine and Protection

摘　　要：目的研究乳化剂吐温-80(Tween-80)对电离辐射诱导胆汁酸肠肝循环障碍的影响。方法48只雄性C57BL/6 J小鼠按照随机数表法分为健康对照组、单纯照射组、照射+Tween-80组和照射+Tween-80+丁酸组,每组12只。采用特制的屏蔽装置及γ射线辐照仪对小鼠进行腹部局部照射。照射前7 d,照射+Tween-80组和照射+Tween-80+丁酸组小鼠每天给予Tween-80灌胃,健康对照组及单纯照射组给予水灌胃;照射后照射+Tween-80+丁酸组每天给予丁酸灌胃直至麻醉处死,健康对照组、单纯照射组和照射+Tween-80组分别每天给予水灌胃直至麻醉处死。照射后21 d,取小鼠小肠及粪便样品,通过酶联免疫吸附试验检测小鼠小肠及粪便中胆汁酸的含量;通过实时定量聚合酶链反应(PCR)检测小肠和(或)结肠样品中TGR5及JAM-A的表达,计算白介素10(IL-10)/白介素12(IL-12)比率的变化;通过免疫组织化学染色比较结肠中GPR43蛋白的含量。结果与单纯照射组相比,Tween-80预处理的受照小鼠小肠中胆汁酸含量进一步降低,粪便中胆汁酸含量升高(7.92%、7.99%,t=3.93、2.94,P<0.05);介导胆汁酸发挥生物学功能的TGR5受体及其下游JAM-A表达水平下降(20.93%、9.91%,t=4.85、5.14,P<0.05)、结肠IL-10/IL-12比率(抗炎指标)降低(4.59%,t=3.39,P<0.05);结肠中能结合短链脂肪酸使其发挥作用的GPR43蛋白表达量降低。丁酸给药使得小鼠小肠胆汁酸含量回升(8.06%,t=9.25,P<0.05)、粪便中胆汁酸含量降低(14.41%,t=4.71,P<0.05);TGR5及JAM-A表达量升高(19.35%、32.71%,t=7.69、19.23,P<0.05),小肠及结肠IL-10/IL-12比率升高(2.39%、4.05%,t=3.38、5.92,P<0.05);结肠中GPR43蛋白含量增加。结论Tween-80加重电离辐射诱导的小鼠胆汁酸肠肝循环障碍,给予丁酸能够改善Tween-80对受照小鼠胆汁酸肠肝循环的抑制作用。Objective To study the effect of emulsifier Tween-80 on radiation-induced bile acid enterohepatic circulation disturbance and the treatment strategy.Methods Male C57BL/6 J mice were randomly divided into healthy control group,radiation-only group,radiation+Tween-80 group and radiation+Tween-80+butyric acid group.The mice were exposed to total abdominal irradiation(TAI)using a specific steel lead chamber andγ-ray irradiator was used throughout the experiments.Mice in radiation+Tween-80 group and radiation+Tween-80+butyric acid group were intragastrically administrated with Tween-80 for 7 d before irradiation,while healthy control group and radiation-only group were treated with sterile water.After irradiation,butyric acid was administrated to mice in radiation+Tween-80+butyric acid group until euthanasia,while healthy control group,radiation-only group and radiation+Tween-80 group were treated with sterile water until euthanasia.Small intestine and fecal particles were collected 21 d after irradiation.The concentrations of bile acid in small intestinal and fecal samples were measured using enzyme linked immunosorbent assay(ELISA),the expression of TGR5 and JAM-A,as well as the ratio of IL-10/IL-12 in intestine were detected by quantitative real-time PCR(qRT-PCR).The expression levels of GPR43 in the colon were compared using immunohistochemistry(IHC).Results Tween-80 pretreated mice exhibited lower concentration of bile acid in small intestine and higher level of bile acid in fecal sample after irradiation(7.92%,7.99%,t=3.93,2.94,P<0.05),the expression of TGR5,which mediating the biological function of bile acid,and it′s downstream JAM-A gene were down-regulated(20.93%,9.91%,t=4.85,5.14,P<0.05),the ratio of IL-10/IL-12(indicator related to inhibition of inflammation)(4.59%,t=3.39,P<0.05)as well as the expression of GPR43 protein,a G-protein-coupled receptor for butyric acid,decreased in the colon of Tween-80-pretreated mice compared with the radiation-only group.ELISA assay revealed that butyric acid administra

关 键 词：腹部局部照射 吐温-80 丁酸 胆汁酸肠肝循环 

分 类 号：R730.55[医药卫生—肿瘤]