目的 观察急性坏死性胰腺炎(ANP)时肠黏膜屏障的损伤情况,以及谷氨酰胺(Gln)和胰岛素样生长因子(IGF)对肠黏膜屏障的保护作用.方法 成功诱导ANP模型雄性Wistar大鼠48只,随机分为ANP组和Gln组各24只,另取假手术组24只作为对照.Gln组每日以Gln灌胃2次,剂量为1.5g/(kg·d);ANP组和假手术组以同等量的生理盐水灌胃.分别在模型制作术后3、6、24、48 h时间点杀死大鼠,取胰头和末端回肠3~5 cm放入液氮中保存.观察胰腺和肠黏膜组织形态学改变,测定肠黏膜中IGF-1的表达、血清中二氨氧化酶(DAO)活性和内毒素浓度.结果 ANP组大鼠肠黏膜屏障功能严重破坏,肠道通透性明显增加,肠黏膜损伤评分明显增加;血清内毒素浓度、DAO活性明显升高(P均<0.01).与ANP组比较,Gln组动物肠黏膜损伤减轻,损伤评分有所下降,血清内毒素水平、DAO活性下降(P均<0.05).ANP组IGF-1表达水平明显下降(P <0.05);Gln组明显升高(P<0.05),同时肠黏膜屏障功能得到一定的改善.结论 ANP时肠黏膜屏障结构和功能存在严重破坏;Gln能一定程度上减轻肠黏膜屏障损伤并能维护其功能;IGF-1参与Gln对ANP肠黏膜屏障损伤的修复和维持.
Objective To observe the injury of intestinal mucosal barrier and the protective action of glutamine (Gln) and insulin-like growth factor 1 (IGF-1) during acute necrotic pancreatitis (ANP).Methods Male Wistar rats which were induced into ANP models (n =48) were randomly divided into two groups,24 rats in each group:ANP group and Gln group,another 24 rats receiving sham operation served as controls (sham operation group).In the ANP group and sham operation group,rats were treated with normal saline,while in the Gln group,rats were treated with Gln by gavage (1.5 g/kg · d).The rats were killed to obtain the head of pancreas and the terminal ileum (3-5 cm) at different time points of 3,6,24 and 48 h,and then we preserved them in liquid nitrogen.During the observation period,the morphological changes of intestinal mucosa and pancreatic tissue were observed,and the concentrations of serum endotoxin and DAO activity were assayed as well as the expression of IGF-1 protein in the mucosal tissue.Results In the ANP group,the intestinal mucosal barrier function was damaged seriously,the intestinal permeability and mucosal injury scores increased,and the concentrations of serum endotoxin and DAO activity were also significantly increased (all P < 0.01).Compared with the ANP group,the injury of intestinal mucosa was attenuated to some extent,the mucosal injury scores decreased,the DAO activity was inhibited,and the mucosal barrier function was improved demonstrated by the decreasing concentrations of serum endotoxin in the Gln group (all P < 0.05).The expression of IGF-1 protein was down-regulated induced by ANP but was upregulated by Gln administration (P < 0.05).Conclusions The intestinal mucosal barrier is damaged during the process of ANP,but Gln alleviates the damage to mucosal barrier and maintains the integrity of mucosal barrier structure and function.Meanwhile,IGF-1 is involved in the protection effect of Gln on intestinal mucosal barrier.