谷氨酰胺对大鼠脑损伤后肠组织炎性信号因子表达的影响

目的 研究大鼠创伤性脑损伤(traumatic brain injury,TBI)后炎性因子在急性肠黏膜损害中的作用,探讨谷氨酰胺(glutamine,Gln)保护肠黏膜结构和屏障功能的可能机制.方法 雄性Wistar大鼠分为对照组、TBI后1,3,5,7 d组和谷氨酰胺干预组,每组6只.应用免疫组化方法测定肠组织中NF-κB的活性,ELISA法测定肠组织中TNF-α、IL-1β的浓度.结果 大鼠TBI后回肠组织中NF-κB活性明显升高,伤后3 d达到峰值,伤后第7天仍保持在较高水平.肠组织IL-1β、TNF-α峰值均出现在伤后1 d,伤后3 d仍保持在较高水平.经胃肠内注入Gln后,NF-κB的活性及TNF-α、IL-1β的浓度与脑损伤后正常进食组比较有明显下降.结论 TBI可引起小肠NF-κB即刻且持久的活性增加以及炎性细胞因子浓度的增高,细胞因子介导的炎性反应可能在急性肠黏膜损害中起重要作用.胃肠内补充谷氨酰胺,可以抑制伤后肠组织NF-κB的活性,降低肠组织炎性细胞因子的浓度.谷氨酰胺可能通过抑制创伤后肠组织的炎症反应来达到保护应激状态下的肠黏膜屏障功能.

Expression changes of intestinal proinflammatory cytokines in response to glutamine following traumatic brain injury in rats

Objective To study the role of the cytokine-mediated inflammation in the pathogenesis of acute intestinal mucosa damage and explore the potential mechanisms of glutamine reducing intestinal inflammatory factors on the intcstines and protecting the structure and barrier of intestinal mucosa after traumatic brain iniury(TBI).Methods A total of 54 male Wistar rats were divided equally into nine groups(6 rats in each group),ie,control group,TBI groups(sacrificed at days 1,3,5 and 7 postinjury,respectively)and Glutamine group.Levels of TNF-α and IL-1β in the intestinal tissues were determined by using ELISA and activity of NF-κB by immunohistochemical method.Results Activity of NF-κB in ileum was significantly increased at day 1 following TBI,reached peak at day 3 and remained hjgh level till at day 7 postinjury.TNF-α and IL-1β levels in the intestinal tissues were also significantly increased after TBI,peaked at day 1 and remained high level at day 3 pestinjury.NF-κB activity and the expressions of TNF-α and IL-1β were all obviously decreased posterior to glutamine administration through stomach tube after TBI,compared with normal foodintake group after TBI.Conclusions TBI can induce a rapid and persistent up-regulation of NF-κB and proinflammatory cytokines in the intestine.Inflammation response may play an important role in the pathogenesis of acute intestinal mucosa injury.Glutamine administration throush stomach tube can inhibit NF-κB activity in ileum and reduce TNF-α and IL-1β levels after TBI,indicating that the intestinal barrier function at stress state may be protected by glutamine administration.