Development of Novel Strategies for Prevention from Bacterial Translocation

出血性休克（HS）是一种氧化应激，导致肠组织损伤。血红素氧合酶（HO）-1是由氧化应激诱导的，被认为在保护组织免受氧化损伤中起重要作用。我们以前报道回肠是HS诱导的肠组织损伤最敏感的部位，因为HO-1诱导在该部位最低。我们先前也证明谷氨酰胺在下肠道中显著诱导HO-1。在本研究中，我们研究了谷氨酰胺预处理是否通过HO-1诱导改善HS诱导的回肠肠组织损伤。谷氨酰胺治疗大鼠显著诱导回肠粘膜上皮细胞中的功能性HO-1蛋白。在HS（平均动脉血压30 mmHg，持续60 min）前给予谷氨酰胺可显著减轻HS诱导的回肠粘膜炎症和凋亡细胞死亡。相反，给予HO活性特异性抑制剂可消除谷氨酰胺预处理的有益作用。这些发现表明谷氨酰胺预处理通过诱导HO-1显著改善HS后回肠的组织损伤。

Hemorrhagic shock (HS) is an oxidative stress which causes intestinal tissue injury. Heme oxygenase (HO)-1 is induced by oxidative stress, and is thought to play an important role in the protection of tissues from oxidative injury. We previously reported the ileum to be the most susceptible to HS-induced tissue injury site in the intestine, because HO-1 induction is the lowest at this site. We also previously demonstrated that glutamine significantly induced HO-1 in the lower intestinal tract. In the present study, we investigated whether glutamine pretreatment improves HS-induced intestinal tissue injury in the ileum by HO-1 induction. Treatment of rats with glutamine markedly induced functional HO-1 protein in mucosal epithelial cells in the ileum. Glutamine treatment before HS (mean arterial blood pressure of 30mmHg for 60min) significantly ameliorated HS-induced mucosal inflammation and apoptotic cell death in the ileum, In contrast, treatment with a specific inhibitor of HO activity, abolished the beneficial effect of glutamine pretreatment. These findings indicate that glutamine pretreatment significantly ameliorated tissue injury in the ileum after HS by inducing HO-1.