DEVELOPMENT AND REPAIR OF MICRO-INJURY IN GASTRIC MUCOSA

在这项资助的支持下，主要研究了局部缺血再灌注(I/R)引起的胃上皮损伤大鼠模型中粘膜微损伤的诱导和修复，在该模型中，损伤通过测量血液到管腔的清除率来定量(Am J PhysIOL 266：G263-270,1994)。动物体温自动控制，腔灌流液由分段收集器收集。使用这一新的系统，评估粘液产生的刺激物(TPA)和粘液剂(N-乙酰-L-半胱氨酸；NAC)的作用，以阐明胃粘液在I/R所致的胃上皮损伤中的作用。TPA减弱和NAC加重的结果强烈表明胃粘液对I/R应激具有保护作用(J Lab Clin Med 126：287-293,1995)。此外，还对内源酸的作用进行了评价。用质子泵抑制剂(奥美拉唑)或H_2受体拮抗剂(T-593)抑制管腔酸度。…更重要的是，这两种药物都显著减弱了I/R引起的清除增加，但是，当鲁米那酸被磷酸盐缓冲盐水灌流完全中和时，清除没有减少。这些数据表明，内源性鲁米酸在胃微损伤中不起重要作用，质子泵抑制剂或H_2受体拮抗剂可能通过降低胃腔酸度以外的机制抑制I/R损伤，即减少胃酸分泌所需的ATP消耗，以改善胃粘膜的能量代谢(J Clin Gasterenterol21：S108-112,1995)。此外，还通过使用眼镜蛇毒素因子(CVF)摄入补体来研究补体在肠缺血后全身休克中的作用。肠I/R组13只大鼠中有2只处死，CVF预处理组无一只死亡。在存活的动物中，观察到I/R期间血压的下降。CVF显著改善了这种血压变化。这些结果表明补体正向参与肠I/R休克，补体也可能参与I/R引起的粘膜损伤。

With a support of this grant, induction and repsir of mucosal micro injury were investigated mainly in a rat model of gastric epithelial damage induced by local ischemial reperfusion (I/R), in which the damage was quantified by measuring the blood-to-lumen ^<51>Cr-EDTA clearance (Am J physiol 266 : G263-270,1994). Animal body temperature was automatically controlled and luminal perfusate was collected by a fraction collector. Using this new system, effects of stimulator of mucus production (tetraprenyl acetone ; TPA) and mucolytic agent (N-acetyl-L-cysteine ; NAC) were assessed to elucidate role of gastric mucus in I/R-induced gastric epithelial injury. The results that TPA attenuated and NAC aggravated ^<51>Cr-EDTA clearance strongly indicate a protective role of gastric mucus against I/R stress (J Lab Clin Med 126 : 287-293,1995). The role of endogenous acid was also evaluated. Proton pump inhibitor (omeprazole) or H_2-receptor antagonist (T-593) wsa used to suppress luminal acidity. … More Both drugs significantly attenuated the increase in clearance induced by I/R.However, when the luminal acid was completely neutralized by luminal perfusion with phosphate-buffered saline, no reduction in clearance was observed. These data indicate that endogenous luminal acid does not play an important role in this gastric micro injury, and that a proton pump inhibitor or H_2-receptor antagonist may suppress I/R injury by a mechanism other than reducing luminal acidity, i.e., reducing consumption of ATP needed for acid secretion to improve gastric mucosal energy metabolism (J Clin Gastroenterol 21 : S108-112,1995). In addition, the role of complement in systemic shock following intestinal ischemia was also investigated by consuming complements using cobra venom factor (CVF). Two out of 13 rats were killed by intestinal I/R.No rat was killed in CVF pretreated group. In survival animals, decrease in blood pressure was observed in I/R.CVF significantly improved this change in blood pressure. These results indicate that complements positively participate in the shock induced by intestinal I/R,and that complements might also participate in mucosal injury induced by I/R. Less