DEVELOPMENT AND REPAIR OF MICRO-INJURY IN GASTRIC MUCOSA

在该基金的支持下，主要在由局部缺血再灌注（I/R）诱导的胃上皮损伤的大鼠模型中研究了粘膜微损伤的诱导和修复，其中通过测量血液到管腔的2Cr-EDTA清除率来量化损伤<51>（Am J Physiol 266：G263- 270，1994）。自动控制动物体温，并通过馏分收集器收集管腔灌注液。使用这个新的系统，粘液产生的刺激剂（四异戊二烯基丙酮; TPA）和粘液溶解剂（N-乙酰-L-半胱氨酸; NAC）的影响进行了评估，以阐明胃粘液在I/R诱导的胃上皮损伤中的作用。TPA减弱和NAC加重1Cr-EDTA清除的结果<51>强烈地表明胃粘液对I/R应激的保护作用（J Lab Clin Med 126：287- 293，1995）。还评价了内源性酸的作用。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。 ...更多信息 这两种药物显着衰减I/R诱导的清除率的增加。然而，当管腔酸完全中和管腔灌注磷酸盐缓冲盐水，没有减少清除率观察。提示内源性管腔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管腔酸以外的机制抑制I/R损伤，减少酸分泌所需的ATP消耗以改善胃粘膜能量代谢（J Clin Gastroenterol 21：S108- 112，1995）。此外，还通过使用眼镜蛇毒因子（CVF）消耗补体来研究补体在肠缺血后系统性休克中的作用。CVF预处理组无大鼠死亡。在存活动物中，在I/R中观察到血压降低。CVF显著改善了血压的这种变化。这些结果表明，补体参与了肠I/R引起的休克，补体还可能参与了肠I/R引起的粘膜损伤。少

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