PATHO-PHYSIOLOGY OF ACUTE ACID INJURY IN RABBIT ESOPHAGEAL EPITHELIUM
PATHO-PHYSIOLOGY OF ACUTE ACID INJURY IN RABBIT ESOPHAGEAL EPITHELIUM
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DOI：
10.1172/jci110246
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发表时间：
1981-01-01
影响因子：
15.9
通讯作者：
CARNEY, CN
中科院分区：
文献类型：
--
作者：
ORLANDO, RC;POWELL, DW;CARNEY, CN
研究了反流性食管炎的病理生理学。本文探讨了急性酸损伤兔食管粘膜结构和功能变化的早期顺序。使用灌注导管技术，在用磷酸盐缓冲盐水或80 mM HCl-80 mM NaCl灌注食管下1/2之前、期间和之后，在麻醉家兔中获得食管电位差（PD）曲线。当酸灌注使食管下段PD降低至初始值的40-50%或80-100%时，取出食管，切片，并采用光学显微镜、透射电子显微镜和Ussing室技术研究粘膜，以评价Na和甘露醇转运。酸损伤早期粘膜阻力降低，Na+和甘露醇被动转运增加（P < 0.05）。在此阶段，短路电流或净钠转运无显著变化，唯一的形态学发现是EM上的细胞间隙扩张。酸损伤的后期表现出电阻的进一步降低，这一发现现在伴随着短路电流的减少和净钠转运的完全抑制。此时的形态学研究显示棘层中细胞坏死、水肿和囊泡形成。明显不存在肉眼粘膜变化和透壁坏死。当食管灌注与酸和胃蛋白酶的组合进行，形态和生理学的结果基本上是相同的，与酸单独的灌注时间达到50%或100%的PD减少缩短。细胞和/或细胞旁渗透性的初始增加，随后抑制主动钠转运可以解释这些发现。渗透调节的丧失导致棘层细胞坏死。
The pathophysiology of reflux esophagitis was studied. The early sequence of changes in mucosal structure and function in acutely acid-damaged rabbit esophagus was sought. Using a perfused catheter technique, esophageal potential difference (PD) profiles were obtained in anesthetized rabbits before, during and after perfusion of the lower 1/2 of the esophagus with phosphate-buffered saline or 80 mM HCl-80 mM NaCl. When acid perfusion reduced the lower esophageal PD by 40-50% or 80-100% of the initial values, the esophagus was removed, sectioned and the mucosa studied with light microscopy, transmission electron microscopy and Ussing chamber technique for evaluation of Na and mannitol transport. The earlier stage of acid damage was associated with reduced mucosal resistance and increased passive transport of Na and mannitol (P < 0.05). There was no significant change in short circuit current or net Na transport at this stage and the only morphologic finding was dilated intercellular spaces on EM. The later stage of acid damage exhibited a further reduction in resistance, a finding now accompanied by a reduction in short circuit current and complete inhibition of net Na transport. Morphologic studies at this time revealed cellular necrosis, edema and vesicle formation in the stratum spinosum. The gross mucosal changes and transmural necrosis were notably absent. When esophageal perfusion was performed with a combination of acid and pepsin, the morphologic and physiologic findings were essentially the same as with acid alone; the time of perfusion to reach the 50 or 100% reduction in PD was shortened. An initial increase in cellular and/or paracellular permeability followed by inhibition of active Na transport can explain these findings. The resulting loss of osmolar regulation leads to cell necrosis in the stratum spinosum.