临床肝胆病杂志2018，Vol.34Issue(6)：1268-1272,5.DOI:10.3969/j.issn.1001-5256.2018.06.027
环境内分泌干扰物双酚A对非酒精性脂肪性肝病大鼠模型肠道黏膜屏障的影响
Influence of bisphenol A on intestinal mucosal barrier in rats with nonalcoholic fatty liver disease
摘要
Abstract
Objective To investigate the influence of bisphenol A ( BPA) , an environmental endocrine disruptor , on inflammatory response in rats with nonalcoholic fatty liver disease ( NAFLD) , as well as its adverse effect on intestinal mucosal barrier .Methods A total of 18 mature male rats were randomly divided into normal group , NAFLD group, and NAFLD+BPA group, with 6 rats in each group.liver patho-logical changes were observed under a light microscope;ELISA was used to measure the serum levels of tumor necrosis factor -α( TNF-α), interleukin-1β(IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8);the terminal colorimetric analysis with Limulus a-mebocyte lysate was used to measure the level of endotoxin;an immunofluorescence assay was used to measure the expression of occluding protein in the intestinal mucosa;real-time PCR was used to measure the mRNA expression of ZO -1 in the intestinal mucosa .A one-way analysis of variance was used for comparison of continuous data between multiple groups , and the SNK-q test was used for further compari-son between two groups .Results Liver pathological examination showed that the rat model of NAFLD was established successfully .After the 8-week treatment with 100 nmol/L BPA, compared with the normal group and the NAFLD group , the NAFLD+BPA group had signifi-cant increases in the expression of TNF -α(127.65 ±22.4 pg/ml vs 64.87 ±10.83 pg/ml and 92.34 ±10.68 pg/ml, P<0.05), IL-6 (199.34 ±17.46 pg/ml vs 91.27 ±9.82 pg/ml and 181.93 ±20.11 pg/ml, P<0.05), and IL-8 (258.79 ±12.82 pg/ml vs 123.76 ± 19.68 pg/ml and 201.64 ±22.34 pg/ml, P<0.05) and the level of endotoxin (0.88 ±0.26 EU/ml vs 0.27 ±0.09 EU/ml and 0.63 ± 0.15 EU/ml, P<0.05).The NAFLD group and the NAFLD+BPA group had a significantly higher level of IL -1βthan the normal group (186.31 ±20.06 pg/ml and 208.78 ±13.77 pg/ml vs 112.84 ±23.12 pg/ml, both P<0.05), but there was no significant difference be-tween these two groups .Compared with the normal group , the NAFLD group and the NAFLD+BPA group had significant reductions in the expression of occluding protein and the mRNA expression of ZO -1 in the intestinal mucosa , and the NAFLD+BPA group had a significantly greater reduction in the mRNA expression of ZO -1 than the control group and the NAFLD group (33.25 ±11.04 vs 68.03 ±11.73/45.24 ± 6.98, P<0.05).Conclusion In the background of NAFLD, long-time exposure to low-dose BPA can increase the release of some in-flammatory factors, promote endotoxemia , and thus damage intestinal mucosal barrier .关键词
非酒精性脂肪性肝病/内分泌干扰物/肠黏膜/大鼠,Sprague-DawleyKey words
nonalcoholic fatty liver disease/endocrine disruptors/intestinal mucosa/rats/Sprague-Dawley分类
医药卫生引用本文复制引用
丁雯瑾,袁涛,沈峰,周达,孙超,范建高,陈源文..环境内分泌干扰物双酚A对非酒精性脂肪性肝病大鼠模型肠道黏膜屏障的影响[J].临床肝胆病杂志,2018,34(6):1268-1272,5.基金项目
国家自然科学基金资助项目(81400610) （81400610）
教育部留学回国人员科研启动基金项目(201404802) （201404802）
上海市卫生和计划生育委员会青年科研项目(20134Y043) （20134Y043）
上海交通大学医工交叉研究基金资助项目(YG2016MS72) （YG2016MS72）
黎介寿院士肠道屏障研究专项基金(LJS_201214,LJS_201319) （LJS_201214,LJS_201319）
