Protection by enteral glutamine is mediated by intestinal epithelial cell peroxisome proliferator-activated receptor-γ during intestinal ischemia/reperfusion.
Protection by enteral glutamine is mediated by intestinal epithelial cell peroxisome proliferator-activated receptor-γ during intestinal ischemia/reperfusion.
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DOI：
10.1097/shk.0000000000000297
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Kozar RA
中科院分区：
文献类型：
--
作者：
Peng Z;Ban K;Wawrose RA;Gover AG;Kozar RA
我们已经证明，肠内谷氨酰胺可以为缺血后的肠道提供保护，而 PPARγ 在这种保护中发挥着作用。使用 Cre/lox 技术生成肠上皮细胞 (IEC) 特异性 PPARγ 无效小鼠模型，我们现在研究了 IEC PPARγ 对谷氨酰胺局部和远端器官保护作用的贡献。这些小鼠肠道中 PPARγ 表达缺失，但其他组织中 PPARγ 表达正常。在异氟烷麻醉下肠道缺血一小时后，野生型和无效小鼠接受肠内谷氨酰胺（60 mM）或载体，然后在生存实验中再灌注 6 小时或 7 天，并与假手术组进行比较。小肠。分析肝脏和肺的损伤和炎症参数。谷氨酰胺对肠道损伤和炎症具有显着的保护作用，对肺和肝脏也有类似的保护作用。全身 TNFα 的变化反映了受损器官中的变化。重要的是，缺乏 IEC PPARγ 的小鼠损伤和炎症恶化，谷氨酰胺失去了对肠道和肺部的保护作用。在谷氨酰胺处理的野生型小鼠中发现的生存益处在无效小鼠中没有观察到。这些研究使用以 IEC 为目标的功能丧失方法，首次在天然小肠和肺部体内证实 PPARγ 负责肠内谷氨酰胺在减少肠道和肺部损伤和炎症以及提高生存率方面的保护作用。这些数据表明，早期肠内谷氨酰胺可能是减少休克引起的肠道功能障碍和随后的远端器官损伤的潜在治疗方式。
We have demonstrated that enteral glutamine provides protection to the post ischemic gut and that PPARγ plays a role in this protection. Using Cre/lox technology to generate an intestinal-epithelial cell (IEC) specific PPARγ null mouse model, we now investigated the contribution of IEC PPARγ to glutamine’s local and distant organ protective effects. These mice exhibited absence of expression of PPARγ in the intestine but normal PPARγ expression in other tissues. Following one hour of intestinal ischemia under isoflurane anesthesia, wild type and null mice received enteral glutamine (60 mM) or vehicle followed by 6 hours of reperfusion or 7 days in survival experiments and compared to shams. Small intestine. liver, and lungs were analyzed for injury and inflammatory parameters. Glutamine provided significant protection against gut injury and inflammation with similar protection in the lung and liver. Changes in systemic TNFα reflected those seen in the injured organs. Importantly, mice lacking IEC PPARγ had worsened injury and inflammation and glutamine lost its protective effects in the gut and lung. The survival benefit found in glutamine treated wild type mice was not observed in null mice. Using an IEC-targeted loss-of-function approach, these studies provide the first in vivo confirmation in native small intestine and lung that PPARγ is responsible for the protective effects of enteral glutamine in reducing intestinal and lung injury and inflammation and improving survival. These data suggest that early enteral glutamine may be a potential therapeutic modality to reduce shock-induced gut dysfunction and subsequent distant organ injury.