IN VITRO STUDIES OF INTESTINAL FLUORIDE ABSORPTION

肠道氟化物吸收的体外研究

• 批准号: 3425008
• 负责人: HAROLD H MESSER
• 金额: $ 2.01万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-02-01 至 1988-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3425008
• 关键词: gastrointestinal absorption /transport; ingested fluoride therapy; membrane permeability; small intestines

Fluoride (F) readily traverses cell membranes and cell layers (e.g., epithelia of the gastrointestinal tract), and this transfer is considered to occur by passive diffusion. The pH dependence of F transfer has led to the proposal that the permeable species is undissociated HF, and that cell membranes are essentially impermeable to fluoride ion F-. This has been demonstrated in bacteria and cell suspensions. An increase in F transfer in response to a lowering of pH has also been shown in renal excretion and in F absorption in the stomach and the urinary bladder. Absorption of F occurs very readily in the small intestine despite the high pH and hence extremely low HF concentration, and the pH dependence of intestinal F absorption has not been subjected to rigorous analysis. This proposal is directed toward the question: Is F transfer across the small intestine directly proportional to undissociated HF concentration? Segments of wall of the small intestine of dogs will be mounted as flat sheets in a two-chamber incubation apparatus, and the transfer of F from the mucosal to the serosal side measured under varying conditions of total E concentration and pH. This is vitro system will be used because it avoids the complexities of whole animal absorption studies and permits precise control of pH and of total F, undissociated HF and fluoride ion F- concentrations. The HF concentration can be calculated under any conditions of pH and total F concentration from the Henderson-Hasselbalch equation. By systematically varying pH and total F concentration, the concentration of undissociated HF can be held constant over a wide range of total F concentration. In addition, the HF and F- concentrations can be manipulated so that they both increase or decrease together, or one may increase while the other decreases. By manipulating the F concentrations and pH on the mucosal side and measuring the rate of F accumulation on the serosal side, the relationship between F transfer and concentrations of the different F species can be investigated.

氟化物 (F) 很容易穿过细胞膜和细胞层（例如， 胃肠道上皮细胞），这种转移被认为是 通过被动扩散发生。 F 转移的 pH 依赖性导致 提议渗透性物质是未解离的 HF，并且该细胞 膜基本上不能渗透氟离子 F-。 这已经是 在细菌和细胞悬浮液中得到证实。 F转移增加 肾脏排泄也显示出对 pH 值降低的反应 F在胃和膀胱中吸收。 F的吸收 尽管 pH 值很高，但在小肠中很容易发生，因此 极低的 HF 浓度，以及肠道 F 的 pH 依赖性 吸收尚未经过严格的分析。 该提案针对的问题是：F是否跨域转移？ 小肠与未解离的 HF 浓度成正比？ 狗的小肠壁片段将被安装成平坦的 两室孵化装置中的片材，以及 F 的转移 在不同条件下测量的粘膜到浆膜侧的总 E浓度和pH值。 将使用体外系统，因为它 避免了整个动物吸收研究的复杂性并允许 精确控制 pH 值以及总 F、未解离的 HF 和氟离子 F- 浓度。 HF浓度可以在任意条件下计算 Henderson-Hasselbalch 的 pH 条件和总氟浓度 方程。 通过系统地改变 pH 值和总氟浓度， 未解离的 HF 浓度可以在很宽的范围内保持恒定 总氟浓度。 此外，HF 和 F- 浓度可以是 进行操纵，使它们同时增加或减少，或者可以 增加，而其他则减少。 通过控制 F 浓度 和粘膜侧的pH值，并测量粘膜侧的F积累率 浆膜侧，F转移与浓度之间的关系 可以研究不同的 F 物种。