| 李源,樊赛军,肖惠文,等.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[J].中华放射医学与防护杂志,2021,41(5):321-326.Li Yuan,Fan Saijun,Xiao Huiwen,et al.Effects of Tween-80 and butyric acid on radiation-induced bile acid enterohepatic circulation disturbance and the treatment strategy[J].Chin J Radiol Med Prot,2021,41(5):321-326 |
| 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 |
| 投稿时间：2020-07-13 |
| DOI：10.3760/cma.j.issn.0254-5098.2021.05.001 |
| 中文关键词: 腹部局部照射 吐温-80 丁酸 胆汁酸肠肝循环 |
| 英文关键词:Local abdominal irradiation Tween-80 Butyric acid Bile acid enterohepatic circulation |
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| 中文摘要: |
| 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。 |
| 英文摘要: |
| 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 and γ-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 administration elevated bile acid level in small intestines (8.06%, t=9.25, P<0.05), but reduced that in feces (14.41%, t=4.71, P<0.05). In addition, TGR5 and JAM-A showed higher expression in the intestine of butyric acid-treated mice (19.35%, 32.71%, t=7.69, 19.23, P<0.05), as well as the ratio of IL-10/IL-12 (2.39%, 4.05%, t=3.38, 5.92, P<0.05) and the content of GPR43 protein in colon. Conclusions Tween-80 deteriorates the disturbance of bile acid enterohepatic circulation induced by ionizing radiation in mice. Butyric acid administration erases the adverse effects of Tween-80. |
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