Orlando R C, Powell D W, Carney C N
J Clin Invest. 1981 Jul;68(1):286-93. doi: 10.1172/jci110246.
To increase our understanding of the pathophysiology of reflux esophagitis, we sought the early sequence of changes in mucosal structure and function in acutely acid-damage rabbit esophagus. Using a perfused catheter technique esophageal potential difference (PD) profiles were obtained in anesthetized rabbits before, during, and after perfusion of the lower one-half of the esophagus with phosphate-buffered saline or 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 sodium and mannitol transport. The earlier stage of acid damage (PD 40-50%) was associated with reduced mucosal resistance fom 2,180 +/- 199 to 673 +/- 157 ohm cm2 and increased passive transport of sodium (0.10 +/- 0.06 to 1.82 +/- 0.48 microeq/h.cm2) and mannitol (0.008 +/- 0.003 to 0.051 +/- 0.012 microM/h.cm2) (p less than 0.05). There was no significant change in shirt circuit current (0.35 +/- 0.05 to 0.35 +/- 0.04) or net sodium transport (0.32 +/- 0.06 to 0.37 +/- 0.12) at this stage, and the only morphologic finding was dilated intercellular spaces on electron microscopy. The later stage of acid damage (PD 80-100%) exhibited a further reduction in resistance to 299 +/- 65 ohm.cm2 (p less than 0.05), a finding now accompanied by a reduction in short circuit current (0.35 +/- 0.05 to 0.21 +/- 0.04 microeq/h.cm2) and complete inhibition of net sodium transport (0.32 +/- 0.06 to 0.01 +/- 0.13) (p less than 0.05). Morphologic studies at this time revealed cellular necrosis, edema, and vesicle formation in the stratum spinosum. Both gross mucosal changes and transmural necrosis were notably absent. When esophageal perfusion was performed with a combination of acid (80 mM HCl-80 mM NaCl) and pepsin (100 microgram/ml), the morphologic and physiologic findings were essentially the same as with acid alone; however, the time of perfusion to reach either the 50 or 100% reduction in PD was shortened. The findings in this model can be explained on an initial increase in cellular and/or paracellular permeability followed by inhibition of active sodium transport. The resulting loss of osmolar regulation leads to cell necrosis in the stratum spinosum.
为了增进我们对反流性食管炎病理生理学的理解，我们探寻了急性酸损伤兔食管黏膜结构和功能变化的早期序列。采用灌注导管技术，在麻醉兔食管下半部用磷酸盐缓冲盐水或80 mM氯化钠灌注前、灌注期间及灌注后，获取食管电位差（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，并用光学显微镜、透射电子显微镜及尤斯灌流小室技术研究黏膜，以评估钠和甘露醇转运。酸损伤的早期阶段（PD 40 - 50%）与黏膜电阻从2,180±199降至673±157 ohm·cm²相关，同时钠（从0.10±0.06增至1.82±0.48微当量/小时·cm²）和甘露醇（从0.008±0.003增至0.051±0.012微摩尔/小时·cm²）的被动转运增加（p＜0.05）。在此阶段，短路电流（从0.35±0.05至0.35±0.04）或净钠转运（从0.32±0.06至0.37±0.12）无显著变化，唯一的形态学发现是电子显微镜下细胞间隙增宽。酸损伤的后期阶段（PD 80 - 100%）电阻进一步降至299±65 ohm·cm²（p＜0.05），此时伴有短路电流降低（从0.35±0.05至0.21±0.04微当量/小时·cm²）及净钠转运完全抑制（从0.32±0.06至0.01±0.13）（p＜0.05）。此时的形态学研究显示棘层细胞坏死、水肿及囊泡形成。明显未见大体黏膜改变及透壁坏死。当用酸（80 mM HCl - 80 mM NaCl）和胃蛋白酶（100微克/毫升）联合进行食管灌注时，形态学和生理学发现与单用酸时基本相同；然而，达到PD降低50%或100%的灌注时间缩短。该模型中的发现可解释为细胞和/或细胞旁通透性最初增加，随后主动钠转运受抑制。由此导致的渗透压调节丧失致使棘层细胞坏死。
