Renal Inner Medulla: Integrated Structure and Function

肾内髓质：综合结构和功能

• 批准号: 6865096
• 负责人: WILLIAM H DANTZLER
• 金额: $ 22.58万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-12-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6865096
• 关键词: biological transport; cell water; chinchilla; immunocytochemistry; kidney function; laboratory rat; mathematical model; membrane permeability; model design /development; osmotic pressure; perfusion; physical model; renal medulla; renal tubule; sodium chloride; structural biology; urea; urine; water channel

DESCRIPTION (provided by applicant): The primary goal is to advance understanding of the functional and structural relationships in the mammalian renal inner medulla by determining the three-dimensional structural organization of the descending and ascending thin limbs of Henle' s loops, collecting ducts, and vasa recta in the inner medulla and the relationship of this structure to integrated function, including the fluxes of urea, inorganic ions, and water, and, thus, development of the inner medullary osmotic gradient. Observations that: 1) many inner medullary thin limbs contain segments of cells with the appearance and function of cells in pure ascending limbs intermixed with segments of cells with the appearance and function of cells in pure descending limbs; 2) the lower 60% of all pure descending thin limbs with bends below the first millimeter of the inner medulla appear to lack water and chloride channels; 3) the inner medullary long descending thin limbs tend to be arranged in a ring-like arrangement around collecting ducts; and 4) the prebend segments are all of similar length and begin abruptly with the appearance of chloride channels suggest that the architectural arrangement of these segments and their transporters and channels may be critical to the development of inner medullary ionic and osmotic gradients. An initial mathematical model supports the latter concept. The planned studies will involve primarily Munich-Wistar rats and take advantage of major developments in techniques for three-dimensional functional reconstruction of tubular structures in the inner medulla and of techniques for studying functions of segments of thin limbs by perfusion in vitro. They will involve 1) complete three-dimensional, quantitative reconstruction of all inner medullary thin limbs of Henle's loops, collecting ducts, and vasa recta from serial sections, using immunocytochemical markers of physiological function to identify tubule segments and tubular sites of transport functions; 2) direct measurements, by in vitro microperfusions, of the urea, NaC1, and water permeabilities of specific thin limb segments defined in the reconstructions; and 3) integration of the function of the inner medullary thin limbs, vasa recta, and collecting ducts in the process of producing a concentrated urine via mathematical modeling based on information obtained from the functional reconstructions and the in vitro microperfusions.

描述（申请人提供）：主要目标是通过确定内髓中Henle袢、集合管和直血管的下降和上升细肢的三维结构组织以及该结构与综合功能的关系，包括尿素、无机离子、和水，并因此，发展的内部骨髓渗透梯度。意见如下：1）许多内髓细肢含有具有纯升肢中细胞的外观和功能的细胞片段，与具有纯降肢中细胞的外观和功能的细胞片段混合; 2）弯曲低于内髓第一毫米的所有纯降肢的下部60%似乎缺乏水和氯离子通道;（3）内髓长降细肢倾向于围绕集合管呈环状排列;和4）预弯曲段都具有相似的长度，并且开始突然出现氯化物通道，这表明这些段及其转运体和通道的结构布置可能对内髓离子和渗透压梯度的发展。最初的数学模型支持后一种概念。计划中的研究将主要涉及Munich-Wistar大鼠，并利用内髓管状结构三维功能重建技术和通过体外灌注研究细肢节段功能的技术的重大发展。它们将包括：1）使用生理功能的免疫细胞化学标记物，从连续切片中对Henle袢、集合管和直血管的所有内髓细肢进行完整的三维定量重建，以识别小管节段和运输功能的小管部位; 2）通过体外微灌注直接测量重建中定义的特定薄肢体节段的尿素、NaCl和水渗透性;以及3）通过基于从功能重建和体外微灌注获得的信息的数学建模，在产生浓缩尿的过程中整合内髓细肢、直血管和集合管的功能。