A research to the participation of endotheline-nitric oxide system in pathophysiology of ischemic disorder of a small intestine and a development for its therapeutic usage.

本实验研究了一氧化氮在大鼠小肠缺血再灌注损伤中的作用，并观察了一氧化氮合酶抑制剂N，G-硝基-L-精氨酸甲酯对小肠缺血再灌注损伤的影响。结扎大鼠肠系膜前动脉60 min，造成短暂性肠缺血，再灌注后5 h测定肠腔灌流液中NO代谢产物（NO_2^-和NO_3^-）和乳酸脱氢酶活性。观察小肠组织学变化的时间进程。缺血再灌注后肠腔一氧化氮释放明显增加，且一氧化氮释放的动力学与乳酸脱氢酶漏出的动力学相关。N，G-硝基-L-精氨酸甲酯（1.0 - 2.5mg/kg）可抑制一氧化氮释放和乳酸脱氢酶漏出的增加，对缺血再灌注引起的粘膜损伤有保护作用。提示小肠缺血再灌注后NO的产生可能参与了肠粘膜的损伤。接下来，我们研究了内皮素受体在大鼠小肠缺血再灌注后，使用定量受体放射自显影方法。与缺血再灌注后小肠粘膜损伤部位相对应，<125>I-内皮素-1结合位点数量增加。这些结合位点是内皮素ETB受体的特征。因此，内皮素系统可能也参与了缺血再灌注损伤后肠粘膜的破坏。这部分的研究现在正在更精确地进行。

We investigated the role of nitric oxide in the mucosal injury induced by ischemia-reperfusion in the rat small intestine and evaluated the effect of N^G-nitro-L-arginine methyl pester, a potent inhibitor of nitric oxide synthase to the ischemia-related injury of the small intestine. A transient intestinal ischemia was produced in the catheterized ileal segments of rats by occluding the anterior mesenteric artery for 60 min. Nitric oxide metabolites (NO_2^- and NO_3^-) and lactate dehydrogenase activity in perfusates of the intestinal lumen were measured over 5 h periods after reperfusion. The time-course of histological changes in small intestine was also observed. After ischemia-reperfusion, nitric oxide release in the intestinal lumen increased significantly and the dynamics of nitric oxide release correlated with that of lactate dehydrogenase leakage. The administration of N^G-nitro-L-arginine methyl ester (1.0 - 2.5 mg/kg) inhibited this increase of the nitric oxide release and the lactate dehydrogenase leakage, and afforded protection against the mucosal injury induced by ischemia-reperfusion. These results suggest that the nitric oxide production which was accelerated by ischemia-reperfusion of small intestine may possibly participate in thc breakdown of intestinal mucosa after ischemia-reperfusion insult. Next, we investigated endothelin receptors in the rat small intestine following ischemia-reperfusion, using a quantitative receptor autoradiographic method. In correspondence to the part of mucosal injury in the small intestine following ischemia-reperfusion ^<125>I-cndothelin-1 binding sites were increased in number. These binding sites were characteristically the endothelin ETB receptor. Thus, endothelin system may also participate in the breakdown of intestinal mucosa after ischemia-reperfusion insult. This part of the research is now go on more precisely.