Machowska A, Brzozowski T, Sliwowski Z, Pawlik M, Konturek P C, Pajdo R, Szlachcic A, Drozdowicz D, Schwarz M, Stachura J, Konturek S J, Pawlik W W
Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Cracow, Poland.
Inflammopharmacology. 2008 Feb;16(1):40-7. doi: 10.1007/s10787-007-1600-6.
Hormonal fluctuations are known to predispose ulceration of the upper gastrointestinal tract, but to date no comparative study of their effects on the healing of pre-existing ulcers in the oral cavity and stomach has been made. We studied the effects of depletion of testosterone and of EGF on the healing of acetic acid-induced ulcers using rats having undergone bilateral orchidectomy and/or salivectomy respectively. We measured alterations in gastric acid secretion and blood flow at ulcer margins, as well as plasma levels of testosterone, gastrin and the proinflammatory cytokines IL-1 beta and TNF-alpha. Testosterone (0.01-10 mg/kg/day i. m.) dose-dependently delayed oral and gastric ulcer healing. When applied in an optimal dose of 1 mg/kg/day, this hormone significantly raised gastric acid secretion and plasma IL-1 beta and TNF-alpha levels. Attenuation of plasma testosterone levels via bilateral orchidectomy inhibited gastric acid secretion and accelerated the healing of oral and gastric ulcers, while increasing plasma gastrin levels and these effects were reversed by testosterone. Salivectomy raised plasma testosterone levels, and delayed oral and gastric ulcer healing. Treatment of salivectomised animals with testosterone further inhibited ulcer healing, and this effect was counteracted by EGF. We propose that testosterone delays ulcer healing via a fall in blood flow at the ulcer margin, a rise in plasma levels of IL-1 beta and TNF-alpha and, in the case of gastric ulcers, an increase in gastric acid secretion. EGF released from the salivary glands plays an important role in limitation of the deleterious effects of testosterone on ulcer healing.
已知激素波动易引发上消化道溃疡，但迄今为止，尚未对其对口腔和胃中已有溃疡愈合的影响进行比较研究。我们分别使用双侧睾丸切除术和/或唾液腺切除术的大鼠，研究了睾酮缺乏和表皮生长因子（EGF）对乙酸诱导溃疡愈合的影响。我们测量了胃酸分泌、溃疡边缘血流量的变化，以及睾酮、胃泌素和促炎细胞因子白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的血浆水平。睾酮（0.01 - 10毫克/千克/天，肌肉注射）剂量依赖性地延迟口腔和胃溃疡的愈合。当以1毫克/千克/天的最佳剂量应用时，这种激素显著提高胃酸分泌以及血浆IL-1β和TNF-α水平。通过双侧睾丸切除术降低血浆睾酮水平可抑制胃酸分泌，并加速口腔和胃溃疡的愈合，同时提高血浆胃泌素水平，而这些作用可被睾酮逆转。唾液腺切除术提高血浆睾酮水平，并延迟口腔和胃溃疡的愈合。用睾酮治疗唾液腺切除的动物进一步抑制溃疡愈合，而这种作用可被EGF抵消。我们认为，睾酮通过降低溃疡边缘的血流量、提高血浆IL-1β和TNF-α水平，以及在胃溃疡的情况下增加胃酸分泌来延迟溃疡愈合。唾液腺释放的EGF在限制睾酮对溃疡愈合的有害作用中起重要作用。
