Liu W, Okajima K, Murakami K, Harada N, Isobe H, Irie T
Department of Laboratory Medicine, Kumamoto University School of Medicine, and the Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
J Lab Clin Med. 1998 Nov;132(5):432-9. doi: 10.1016/s0022-2143(98)90114-7.
Activated neutrophils play an important role in tissue injury by releasing various inflammatory mediators capable of damaging endothelial cells. To investigate whether neutrophil elastase (NE) is involved in stress-induced gastric mucosal injury, we examined the effects of 2 NE inhibitors (ONO-5046 and L-658 758) as well as nitrogen mustard-induced leukocytopenia on the formation of gastric mucosal lesions, gastric mucosal blood flow, gastric mucosal microvascular permeability, and gastric neutrophil accumulation in rats subjected to water immersion-restraint stress (WIR). Gastric mucosal injury peaked 8 hours after WIR. Gastric mucosal blood flow, as measured by laser-Doppler flow cytometry, decreased to 45% of its initial level 8 hours after WIR. Gastric mucosal microvascular permeability, evaluated by Evans blue dye leakage to the gastric mucosa, showed an increase, peaking 8 hours after WIR. Gastric accumulation of neutrophils, determined by measuring gastric myeloperoxidase activity and by histologic examination, was also significantly increased 8 hours after WIR. Both of the NE inhibitors markedly prevented the formation of gastric mucosal lesions. They also decreased the reduction in gastric mucosal blood flow seen in animals subjected to WIR while preventing increases in gastric mucosal microvascular permeability. Gastric neutrophil accumulation was significantly reduced in animals given either inhibitor 8 hours after WIR. Leukocytopenia produced effects similar to those produced by the inhibitors. Taken together, these observations strongly suggest that NE promotes stress-induced gastric mucosal injury in rats by reducing gastric mucosal blood flow and increasing neutrophil accumulation.
活化的中性粒细胞通过释放各种能够损伤内皮细胞的炎症介质，在组织损伤中发挥重要作用。为了研究中性粒细胞弹性蛋白酶（NE）是否参与应激诱导的胃黏膜损伤，我们检测了两种NE抑制剂（ONO - 5046和L - 658 758）以及氮芥诱导的白细胞减少对水浸束缚应激（WIR）大鼠胃黏膜损伤形成、胃黏膜血流量、胃黏膜微血管通透性和胃中性粒细胞积聚的影响。胃黏膜损伤在WIR后8小时达到峰值。通过激光多普勒血流仪测量，胃黏膜血流量在WIR后8小时降至初始水平的45%。通过伊文思蓝染料渗漏至胃黏膜来评估胃黏膜微血管通透性，结果显示其增加，在WIR后8小时达到峰值。通过测量胃髓过氧化物酶活性和组织学检查确定，WIR后8小时胃中性粒细胞积聚也显著增加。两种NE抑制剂均显著预防了胃黏膜损伤的形成。它们还减少了WIR动物胃黏膜血流量的降低，同时防止胃黏膜微血管通透性增加。在WIR后8小时给予任何一种抑制剂的动物中，胃中性粒细胞积聚均显著减少。白细胞减少产生的效果与抑制剂相似。综上所述，这些观察结果强烈表明，NE通过减少胃黏膜血流量和增加中性粒细胞积聚，促进大鼠应激诱导的胃黏膜损伤。
