Abstract：
To investigate fluoride (F)-induced intestine barrier damage and the role of estrogen deficiency in this progress, a rat model of estrogen deficiency was established through bilateral surgical removal of ovaries. The F exposure model was then continued by adding sodium fluoride (0, 25, 50, and 100 mg/L, calculated on a fluorine ion basis) to drinking water for 90 days. Afterward, intestinal mucosal structure, barrier function, and inflammatory cytokines were evaluated. The results showed that excessive F decreased the developmental parameters (crypt depth) of the cecum and rectum and inhibited the proliferation capacity of the intestinal epithelia, which are more obvious in the state of estrogen deficiency. The distribution of goblet cells and glycoproteins in the intestinal mucosa decreased with the increase in F concentration, and estrogen deficiency led to a further decline, especially in the rectum. Using the immunofluorescence method, the study showed that excessive F caused interleukin-17A (IL-17A) significantly decrease in the cecum and increase in the rectum. Meanwhile, F treatment remarkably upregulated the expression of intestinal IL-1β, IL-23, and IL-22, while the level of IL-6 was downregulated. In addition, estrogen deficiency increased IL-1β, IL-6, IL-23, and IL-22, but decreased IL-17A expression in the cecum and rectum. Collectively, F exposure damaged intestinal morphological structure, inhibited epithelial cell proliferation and mucus barrier function, and resulted in the disturbance of T helper (Th) 17 cell-related cytokines expression. Estrogen deficiency may further aggravate F-induced damage to the cecum and rectum.
摘要：
探讨氟(F)诱导的肠屏障损伤及雌激素缺乏在其中的作用。通过双侧卵巢手术切除建立了雌激素缺乏的大鼠模型。然后通过添加氟化钠（0、25、50和100mg/L，以氟离子为基础计算)到90天的饮用水中。之后,肠粘膜结构，屏障功能，和炎性细胞因子进行评估。结果表明，过量的F降低了盲肠和直肠的发育参数(隐窝深度)，抑制了肠上皮细胞的增殖能力，这在雌激素缺乏状态下更为明显。杯状细胞和糖蛋白在肠粘膜中的分布随着F浓度的增加而减少，雌激素缺乏导致进一步下降，尤其是在直肠。使用免疫荧光方法，研究表明，过量的F导致盲肠白细胞介素-17A（IL-17A）显着减少，直肠增加。同时,F处理显著上调肠道IL-1β的表达,IL-23和IL-22，而IL-6的水平下调。此外,雌激素缺乏增加IL-1β，IL-6，IL-23和IL-22，但降低盲肠和直肠中IL-17A的表达。总的来说，F暴露损伤肠道形态结构，抑制上皮细胞增殖和粘液屏障功能，并导致T辅助（Th）17细胞相关细胞因子表达紊乱。雌激素缺乏可进一步加重F诱导的盲肠和直肠损伤。
