Omata Jiro, Fukatsu Kazuhiko, Ueno Chikara, Maeshima Yoshinori, Saitoh Daizoh, Mochizuki Hidetaka
Department of Surgery, National Defense Medical College, Tokorozawa, Japan.
J Surg Res. 2007 Dec;143(2):260-4. doi: 10.1016/j.jss.2006.12.004. Epub 2007 Sep 10.
Glutamine (GLN) treatment prior to gut ischemia-reperfusion (I/R) reportedly preserves gut glutathione levels and gut barrier function. We hypothesized that intraluminal GLN during ischemia would also protect against gut I/R.
After randomization to control and GLN groups, mice were exposed to 75 min (Exp 1) or 50 min (Exp 2 and 3) gut I/R. One mL of 2% GLN solution was injected into the duodenal lumen at the onset of ischemia in the GLN group, whereas controls were given normal saline. In experiment 1, survival was monitored for 120 h (n = 38). In experiment 2, blood, small intestine, and liver samples were collected at 4 h after reperfusion (n = 13). Expressions of CD11a and CD11b on myeloid cells were measured. Reactive oxygen intermediate production by myeloid cells was determined with or without phorbol myristate acetate stimulation. Glutathione levels in the small intestine and liver were also evaluated. In experiment 3, hemodynamic parameters were measured before and after I/R (n = 6).
In experiment 1, survival time in the GLN group was reduced compared with the control group. In experiment 2, GLN increased expression of CD11b and reactive oxygen intermediate with phorbol myristate acetate, compared with controls. There were no significant differences in gut or liver glutathione levels between the two groups. In experiment 3, the GLN group showed a transient but significant reduction in systolic blood pressure after reperfusion compared with the control group.
Intraluminal GLN during severe gut ischemia worsens outcomes, possibly by enhancing circulating myeloid cell priming and activation, and by disturbing hemodynamics, without increasing organ glutathione levels.
据报道，在肠道缺血再灌注（I/R）之前进行谷氨酰胺（GLN）治疗可维持肠道谷胱甘肽水平和肠道屏障功能。我们推测，缺血期间肠腔内给予GLN也可预防肠道I/R。
将小鼠随机分为对照组和GLN组后，使其经历75分钟（实验1）或50分钟（实验2和3）的肠道I/R。在GLN组缺血开始时，向十二指肠腔内注射1 mL 2%的GLN溶液，而对照组给予生理盐水。在实验1中，监测120小时的存活率（n = 38）。在实验2中，再灌注后4小时采集血液、小肠和肝脏样本（n = 13）。测量髓样细胞上CD11a和CD11b的表达。在有或没有佛波酯肉豆蔻酸酯乙酸盐刺激的情况下，测定髓样细胞产生的活性氧中间体。还评估了小肠和肝脏中的谷胱甘肽水平。在实验3中，测量I/R前后的血流动力学参数（n = 6）。
在实验1中，GLN组的存活时间比对照组缩短。在实验2中，与对照组相比，GLN增加了佛波酯肉豆蔻酸酯乙酸盐刺激下CD11b的表达和活性氧中间体的产生。两组之间肠道或肝脏谷胱甘肽水平无显著差异。在实验3中，与对照组相比，GLN组再灌注后收缩压出现短暂但显著的降低。
严重肠道缺血期间肠腔内给予GLN会使结果恶化，可能是通过增强循环髓样细胞的启动和激活以及扰乱血流动力学，而不增加器官谷胱甘肽水平。
