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

丁雯瑾; 袁涛; 沈峰; 周达; 孙超; 范建高; 陈源文

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

DOI: 10.3969/j.issn.1001-5256.2018.06.027

1. 上海交通大学医学院附属新华医院消化科
2. 上海交通大学环境科学与工程学院

基金项目:

国家自然科学基金资助项目(81400610)；教育部留学回国人员科研启动基金项目(201404802)；上海市卫生和计划生育委员会青年科研项目(20134Y043)；上海交通大学医工交叉研究基金资助项目(YG2016MS72)；黎介寿院士肠道屏障研究专项基金(LJS_201214,LJS_201319)；

详细信息

中图分类号: R-332;R575.5
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出版历程
- 收稿日期: 2017-12-19
- 出版日期: 2018-06-20

Influence of bisphenol A on intestinal mucosal barrier in rats with nonalcoholic fatty liver disease

Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Research funding:

摘要

摘要:
目的研究环境内分泌干扰物双酚A（BPA）对非酒精性脂肪性肝病（NAFLD）大鼠炎症反应的影响,以及对肠道黏膜屏障的损害作用。方法将18只成熟雄性SD大鼠随机分为3组:正常组、NAFLD组和NAFLD+BPA组,每组6只。光镜下观察肝脏病理改变,ELISA检测血清TNFα、IL-1β、IL-6和IL-8等炎症因子,鲎试剂终点比色法检测内毒素水平,免疫荧光法观察肠道黏膜Occludin蛋白的表达情况,及实时聚合酶链式反应测定肠道黏膜外周蛋白ZO-1 mRNA的改变。计量资料多组间比较采用单因素方差分析,进一步两两比较用SNK-q检验。结果肝脏病理学证实NAFLD模型建模成功。100 nmol/L BPA摄入8周后,TNFα、IL-6、IL-8炎症因子表达上调[分别为（127.65±22.40）pg/ml、（199.34±17.46）pg/ml和（258.79±12.82）pg/ml]伴内毒素水平增高[（0.88±0.26）EU/ml],与正常组[分别为（64.87±10.83）pg/ml、（91.27±9.82）pg/ml、（123.76±19.68）pg/ml和（0.27±0.09）EU...
- 非酒精性脂肪性肝病 /
- 内分泌干扰物 /
- 肠黏膜 /
- 大鼠,Sprague-Dawley
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 pathological 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 amebocyte 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 comparison 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 significant 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-1β than 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 between 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 inflammatory factors, promote endotoxemia, and thus damage intestinal mucosal barrier.
- nonalcoholic fatty liver disease /
- endocrine disruptors /
- intestinal mucosa /
- rats, Sprague-Dawley

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参考文献(21)

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