Henan Key Laboratory of Environmental and Animal Product Safety, Henan University of Science and Technology, Luoyang 471000, Henan, People's Republic of China.
Ecotoxicol Environ Saf. 2022 Nov;246:114181. doi: 10.1016/j.ecoenv.2022.114181. Epub 2022 Oct 14.
To investigate the effect of estrogen deficiency on the small intestinal mucosal barrier induced by fluoride (F), F exposure models of ovariectomy (OVX) rats (surgically removed ovaries) and non-OVX rats (normal condition) were established by adding sodium fluoride (NaF) (0, 25, 50, and 100 mg/L, calculated by F ion) in drinking water for 90 days. The intestinal mucosal histomorphology, mucosal barrier function, and protein expression levels of tight junctions (TJs), adhesion junctions (AJs), and desmosomes were evaluated in the duodenum, jejunum, and ileum. Hematoxylin-eosin (HE) staining and 5-Bromo-2-deoxyUridine (BrdU) measurement showed that excessive F-induced damage to intestinal epithelial cells and inhibited the proliferation of intestinal epithelial cells, eventually decreasing the number of goblet cells and decreasing glycoprotein secretion, as indicated by Alcian blue and periodic acid-Schiff (AB-PAS) and periodic acid-Schiff (PAS) staining. Further immunofluorescence analysis demonstrated that excessive F decreased the protein expression levels of occludin, zonula occludens-1 (ZO-1), E-cadherin, and desmoplakin (P < 0.05, P < 0.01) and enhanced the expression of claudin-2 (P < 0.01), suggesting that cell-to-cell junctions were disrupted. Collectively, F exposure impaired the small intestinal mucosal barrier by inducing damage to intestinal epithelial cells and inhibiting intestinal epithelial cell proliferation. Disorders in the junctional complex protein expression blocked the synergy between intercellular communication and aggravated mucosal injury. In particular, estrogen deficiency exacerbated F-induced enterotoxicity, which provides new explanations for the development and severity of intestinal disease in postmenopausal women with high-F areas.
为了研究雌激素缺乏对氟（F）诱导的小肠黏膜屏障的影响，通过在饮用水中添加氟化钠（NaF）（0、25、50 和 100 mg/L，以 F 离子计算）建立了去卵巢（OVX）大鼠（手术切除卵巢）和非 OVX 大鼠（正常条件）的 F 暴露模型，共 90 天。评估了十二指肠、空肠和回肠的肠道黏膜组织形态、黏膜屏障功能以及紧密连接（TJs）、黏附连接（AJs）和桥粒的蛋白表达水平。苏木精-伊红（HE）染色和 5-溴-2-脱氧尿苷（BrdU）测量显示，过量 F 诱导的肠道上皮细胞损伤并抑制了肠道上皮细胞的增殖，最终减少了杯状细胞的数量，并降低了糖蛋白分泌，这通过阿尔辛蓝和过碘酸-希夫（AB-PAS）和过碘酸-希夫（PAS）染色显示。进一步的免疫荧光分析表明，过量 F 降低了紧密连接蛋白（occludin、zonula occludens-1 [ZO-1]、E-钙黏蛋白）和桥粒蛋白（desmoplakin）的蛋白表达水平（P<0.05，P<0.01），并增强了 Claudin-2 的表达（P<0.01），表明细胞-细胞连接被破坏。总的来说，F 暴露通过诱导肠道上皮细胞损伤和抑制肠道上皮细胞增殖来破坏小肠黏膜屏障。连接复合体蛋白表达紊乱阻断了细胞间通讯的协同作用，加剧了黏膜损伤。特别是，雌激素缺乏加剧了 F 诱导的肠毒性，这为高氟地区绝经后妇女肠道疾病的发展和严重程度提供了新的解释。
