Sarosiek J, Yu Z, Namiot Z, Rourk R M, Hetzel D P, McCallum R W
University of Virginia Health Sciences Center, Charlottesville.
Am J Gastroenterol. 1994 Apr;89(4):588-94.
Although the prostaglandin-mediated mucosal protection within the gastric compartment has been well established, its potential role in the maintenance of integrity of the esophageal mucosa in humans has not been explored due to the lack of appropriate methodology.
We have recently developed an esophageal perfusion catheter, equipped with two balloons, compartmentalizing a 7.5-cm segment of the esophageal lumen. Using this catheter, we studied the impact of the luminal perfusion with saline, HCl (0.01 M, pH 2.1), and HCl/pepsin solutions (0.5 mg/ml) on esophageal luminal release of PGE2 in 21 asymptomatic, presumably healthy volunteers (12 M, 9F; mean age 40 yr). The content of PGE2 in its methyl oximated form was measured by RIA (Amersham, IL), using a novel iodinated label. Results are expressed as mean +/- SEM. Student's t test was used for statistical analysis.
Perfusion of the esophageal lumen resulted in continuous release of PGE2 into the perfusate at the rate of 1880 +/- 393 pg/min during the first 8-min perfusion period. During continuation of perfusion with saline, the luminal release of PGE2 was maintained at the rate of 1820 +/- 640 pg/min during the second 8-min perfusion period. This rate declined (although in nonsignificant fashion; p < 0.2) during the third perfusion period, reaching a plateau of 1220 +/- 473 pg/min and maintained during the last (period IV) perfusion period with saline. Introduction of acid during the perfusion period II in the second group of investigated subjects resulted in a rapid and statistically significant decline of the luminal release of PGE2 to the value of 1020 +/- 167 ng/min (p < 0.01). Continuation of esophageal perfusion with acid during the next 8-min perfusion period further diminished the luminal release of PGE2 to the value of 520 +/- 73; p < 0.001. The significant decline in the rate of luminal PGE2 release was still maintained despite the replacement of acid with saline during the ending 8-min perfusion (period IV; 560 +/- 80 ng/min; p < 0.001). Esophageal perfusion with HCl/pepsin solution, in group III subjects, potentiated luminal release of PGE2, reaching the value of 1553 +/- 340 pg/min, which is 3 times higher than the value of PGE2 observed during corresponding perfusion with HCl (period III; p < 0.03). This significant impact of HCl/pepsin solution was still maintained despite the substitution of HCl/pepsin with NaCl during the last perfusion period, and was still significantly higher (1260 +/- 220 pg/min; p < 0.02) than the corresponding value during the ending perfusion with NaCl after HCl (group II). This study for the first time demonstrates that luminal release of PGE2 in humans remains under a significant impact of luminal chemical factors such as acid and pepsin.
The modulatory effect of acid and pepsin on esophageal mucosal prostaglandin release may play a role in the development of reflux-related mucosal pathology.
尽管前列腺素介导的胃内黏膜保护作用已得到充分证实，但由于缺乏合适的方法，其在维持人类食管黏膜完整性方面的潜在作用尚未得到探索。
我们最近开发了一种配备两个气囊的食管灌注导管，可将食管腔的7.5厘米段分隔开来。使用该导管，我们研究了向21名无症状、推测健康的志愿者（12名男性，9名女性；平均年龄40岁）的食管腔内灌注生理盐水、盐酸（0.01M，pH 2.1）和盐酸/胃蛋白酶溶液（0.5mg/ml）对食管腔内前列腺素E2（PGE2）释放的影响。采用一种新型碘化标记物，通过放射免疫分析法（RIA，美国伊利诺伊州阿默舍姆公司）测定甲氧肟化形式的PGE2含量。结果以平均值±标准误表示。采用学生t检验进行统计分析。
食管腔灌注导致在最初8分钟灌注期内，PGE2以1880±393 pg/分钟的速率持续释放到灌流液中。在继续用生理盐水灌注期间，在第二个8分钟灌注期内，PGE2的腔内释放速率维持在1820±640 pg/分钟。在第三个灌注期内该速率下降（尽管无统计学意义；p<0.2），降至1220±473 pg/分钟的平台期，并在最后（第四期）用生理盐水灌注期间维持该水平。在第二组被研究对象的灌注期II引入酸后，PGE2的腔内释放迅速且有统计学意义地下降至1020±167 ng/分钟（p<0.01）。在接下来的8分钟灌注期内继续用酸进行食管灌注，进一步使PGE2的腔内释放降至520±73；p<0.001。尽管在最后的8分钟灌注（第四期）期间用生理盐水替代了酸，但腔内PGE2释放速率的显著下降仍得以维持（560±80 ng/分钟；p<0.001）。在第三组对象中，用盐酸/胃蛋白酶溶液进行食管灌注增强了PGE2的腔内释放，达到1553±340 pg/分钟，这比在用盐酸进行相应灌注期间（第三期）观察到的PGE2值高3倍（p<0.03）。尽管在最后灌注期用氯化钠替代了盐酸/胃蛋白酶溶液，但盐酸/胃蛋白酶溶液的这种显著影响仍得以维持，并且仍显著高于在用盐酸灌注后最后用氯化钠灌注期间（第二组）的相应值（1260±220 pg/分钟；p<0.02）。本研究首次证明，人体食管腔内PGE2的释放仍受到腔内化学因素如酸和胃蛋白酶的显著影响。
酸和胃蛋白酶对食管黏膜前列腺素释放的调节作用可能在反流相关黏膜病变的发生中起作用。
