Background and Aim: We hypothesize that selectins, which are adhesion molecules, are involved in the pathogenesis of stress-induced gastropathy. We therefore investigated whether the novel Sialyl Lewis X (SLe(x) ) analog, which is a clinically available antagonist of selectins, attenuate gastric mucosal lesions induced by thermal injury.
Methods: Male Wistar rats were anesthetized and a 30% full-skin thickness dorsal burn was inflicted on each rat. The SLe(x) analog was administrated into the jugular vein 30 min before and 2.5 h after the thermal injury. Saline was administered to the vehicle group. The distribution of E-selectin immunoreactivity on the luminal side of the gastric mucosal microvascular network was observed by immunohistochemical methods . Active oxygen species were measured by the chemiluminescence method. Rolling leukocytes and endothelial damage, investigated by using Monastral Blue B (MBB), of the gastric mucosal microvascular network were observed through an intravital microscope.
Results: A high intensity of E-selectin fluorescence was observed on the luminal surface of the venular endothelial cells 5 h after thermal injury in the vehicle group. However, E-selectin-associated fluorescence was almost negligible in the non-injury group and in the SLe(x) analog group. The SLe(x) analog also attenuated the rolling of leukocytes in the venules, venular deposits of MBB, luminol-dependent chemiluminescence activities, and gastric mucosal lesion formation.
Conclusion: It is suggested that the selectin family is involved in gastric microcirculatory disturbance and the pathogenesis of gastric mucosal lesions after thermal injury. A novel preventive therapy using the SLe(x) analog is considered to effectively protect both gastric microcirculation and the gastric mucosa in rats with thermal injury.(C) 2003 Blackwell Publishing Asia Pty Ltd.