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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
文章发布日期:2018年05月07日  来源:  作者:丁雯瑾,袁涛,沈峰,等  点击次数:571次  下载次数:46次

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【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/ml]及NAFLD组[分别为(92.34±10.68 )pg/ml、(181.93±20.11) pg/ml、(201.64±22.34) pg/ml和(0.63±0.15) EU/ml]相比,差异均有统计学意义(P值均<0.05)。NAFLD组和NAFLD+BPA组中的IL-1β水平明显高于正常组[(18631±20.06)pg/ml、(208.78±13.77)pg/ml) vs (112.84±23.12)pg/ml,P值均<0.05],但NAFLD组和NAFLD+BPA组间差异无统计学意义。此外,与正常组比较,NAFLD组和NAFLD+BPA组中肠道紧密连接蛋白Occludin水平下降,肠道黏膜外周蛋白ZO-1 mRNA表达水平呈显著降低,BPA干预促进ZO-1 mRNA进一步下调(68.03±11.73、45.24±6.98、33.25±11.04,两两组间比较,P值均<0.05)。结论在NAFLD背景下,长期低剂量BPA的暴露能加重炎症因子释放,促进内毒素血症,进而损伤肠道黏膜屏障。
【Abstract】:ObjectiveTo 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. MethodsA 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. ResultsLiver 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). ConclusionIn 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.
【关键字】:非酒精性脂肪性肝病; 内分泌干扰物; 肠黏膜; 大鼠, Sprague-Dawley
【Key words】:nonalcoholic fatty liver disease; endocrine disruptors; intestinal mucosa; rats, Sprague-Dawley
【引证本文】:
DING WJ, YUAN T, SHEN F, et al. Influence of bisphenol A on intestinal mucosal barrier in rats with nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2018, 34(6): 1268-1272. (in Chinese) 丁雯瑾, 袁涛, 沈峰, 等. 环境内分泌干扰物双酚A对非酒精性脂肪性肝病大鼠肠道黏膜屏障的影响[J]. 临床肝胆病杂志, 2018, 34(6): 1268-1272.

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