PREVENTION OF HEMORRHAGIC SHOCK-INDUCED INTESTINAL TISSUE INJURY BY GLUTAMINE VIA HEME OXYGENASE-1 INDUCTION
PREVENTION OF HEMORRHAGIC SHOCK-INDUCED INTESTINAL TISSUE INJURY BY GLUTAMINE VIA HEME OXYGENASE-1 INDUCTION
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DOI：
10.1097/shk.0b013e318177823a
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发表时间：
2009-01-01
期刊：
影响因子：
3.1
通讯作者：
Morita, Kiyoshi
中科院分区：
文献类型：
--
作者：
Umeda, Kana;Takahashi, Toru;Morita, Kiyoshi
出血性休克（HS）是一种氧化应激，导致肠组织损伤。血红素加氧酶1（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。我们以前也证明，谷氨酰胺（GLN）显着诱导HO-1在下肠道。在本研究中，我们研究了GLN预处理是否通过HO-1诱导改善HS诱导的回肠肠组织损伤。用GLN（0.75 g/kg，i.v.）显著诱导回肠粘膜上皮细胞中的功能性HO-1蛋白。HS前谷氨酰胺治疗（MAP 30 mmHg，持续60分钟）显着改善HS诱导的回肠粘膜炎症和凋亡细胞死亡，这是通过TNF-α、iNOS、细胞间粘附分子1和血管细胞粘附分子1的基因表达、髓过氧化物酶活性显着降低来判断的。浸润的中性粒细胞数量，原位寡聚连接分析的DNA片段化，并激活caspase-3的表达，并通过增加IL-10和Bcl-2的基因表达。与此相反，治疗与锡mesoporphyrin，HO活性的特异性抑制剂，取消了GLN预处理的有益效果。这些结果表明，GLN预处理显着改善组织损伤后，HS诱导HO-1的回肠。因此，谷氨酰胺治疗可以通过HO-1的抗炎和抗凋亡特性保护粘膜细胞免受HS诱导的氧化损伤。
Hemorrhagic shock (HS) is an oxidative stress that causes intestinal tissue injury. Heme oxygenase 1 (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 (GLN) significantly induced HO-1 in the lower intestinal tract. In the present study, we investigated whether GLN pretreatment improves HS-induced intestinal tissue injury in the ileum by HO-1 induction. Treatment of rats with GLN (0.75 g/kg, i.v.) markedly induced functional HO-1 protein in mucosal epithelial cells in the ileum. Glutamine treatment before HS (MAP of 30 mmHg for 60 min) significantly ameliorated HS-induced mucosal inflammation and apoptotic cell death in the ileum, as judged by significant decreases in gene expression of TNF-alpha, iNOS, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1, myeloperoxidase activity, the number of infiltrated neutrophils, DNA fragmentation by in situ oligo ligation assay, and activated caspase-3 expression, and by increases in gene expression of IL-10 and Bcl-2. In contrast, treatment with tin mesoporphyrin, a specific inhibitor of HO activity, abolished the beneficial effect of GLN pretreatment. These findings indicate that GLN pretreatment significantly ameliorated tissue injury in the ileum after HS by inducing HO-1. Glutamine treatment may thus protect mucosal cells from HS-induced oxidative damage via the anti-inflammatory and antiapoptotic properties of HO-1.