高血糖素样肽2对大鼠严重脑外伤后肠道免疫功能的影响

Effects of glucagon-like peptide 2 on intestinal immunity of rats following severe traumatic brain injury

目的:了解高血糖素样肽2对大鼠严重脑外伤后胆汁中分泌型IgA、肠黏膜蛋白质和DNA含量、门静脉血内毒素含量的影响。方法:实验于2003-07/2005-07在上海交通大学医学院附属第三人民医院神经外科实验室完成。①分组:健康雄性SD大鼠18只,随机(随机数字法)分为对照组、损伤组和高血糖素样肽2组,每组6只。②模型制备:戊巴比妥钠(50mg/kg)腹腔注射麻醉后,在大鼠右侧颅顶部用牙科钻钻开一直径为5mm的骨窗,注意保持硬膜完整,参考袁氏自由落体脑挫裂伤模型造成右顶叶较为一致的脑挫裂伤,冲击力为100g×15cm。对照组只行开颅,不进行打击。③高血糖素样肽2组大鼠在脑挫裂伤后腹腔注射高血糖素样肽2,按每天15g/kg的剂量分两次腹腔注射,间隔10～12h,连续注射7d。损伤组相同时间点腹腔注射相同剂量生理盐水。④连续注射7d后收集各组大鼠胆汁测定分泌型IgA、采集门静脉血测定血内毒素及制备小肠黏膜标本测定小肠黏膜蛋白质和DNA含量。结果:18只大鼠均进入结果分析。①损伤组胆汁中sIgA水平[(97.0±8.5)mg/L]仅为对照组[(119.7±10.8)mg/L]的81%左右(P<0.05),高血糖素样肽2组[(114.3±10.9)mg/L]与对照组接近(P>0.05)。②高血糖素样肽2组小肠黏膜蛋白质和DNA含量高于损伤组[蛋白质:(2.3±0.1),(2.1±0.1)mg/cm;DNA:(154.3±13.8),(143.4±10.1)mg/L,P均<0.05],与对照组[(2.4±0.1)mg/cm,(163.8±14.9)mg/L]接近。③高血糖素样肽2组门静脉血内毒素含量低于损伤组[(82.8±6.3),(90.1±7.8)Eu/L,P<0.05],与对照组[(78.9±5.4)Eu/L]接近。结论:高血糖素样肽2能够改善严重脑外伤后肠道免疫功能,从而减轻内毒血症。

AIM： To investigate the effect of glucagon-like peptide-2 （GLP-2） on the concentration of slgA in bile, content of protein and DNA in intestinal mucosa, and the content of endotoxin in portal blood of rats with severe traumatic brain injury. METHODS： The experiment was conducted in the Laboratory of Neurosurgery, Third People＇s Hospital Affiliated to the Medical College of Shanghai Jiao Tong University from July 2003 to July 2005. ①Grouping： Eighteen male SD rats were randomly assigned to control group, traumatic group and GLP-2 group with 6 rats in each group. ②Model establishment： Rats were anesthetized by abdominally injected with pentobarbital sodium （50 mg/kg） and then a 5-mm bone window was made with dental drill at the top of right skull with the dura kept complete. Models of impact brain injury （CCI） in were induced by free-falling with the impact of 100 gxl 5 cm. Rats in the control group were only opened the skull without impact. ③Rats in GLP-2 group were abdominally injected with GLP-2 following CCI twice a day at the dose of 15 g/kg with an interval of 10-12 hours for 7 continuous days. Rats in the injury traumatic group were abdominally injected with normal saline at the same time-points and dose. ④The slgA of bile and endotoxin of portal blood were collected to prepare for intestinal mucosal specimens and determine the protein and DNA content in it. RESULTS： A total of 18 rats were involved in the analysis of results： ①The level of slgA of bile in traumatic group [（97.0±8.5） mg/L] was about 81% of that in the control group [（119.7±10.8） mg/L, P 〉 0.05], while that in GLP-2 group [（114.3±10.9） mg/L] was similar to that in the control group （P 〉 0.05）. ②DNA and protein contents in intestinal mucosa in the GLP-2 group were significantly higher than those in the traumatic group [protein： （2.3±0.1）, （2.1±0.1） mg/cm; DNA： （154.3±13.8）, （143.4±10.1） mg/L, all P 〈 0.05], while they were similar to those in the control group [（2.4±0.1） mg/cm, （163.8±14.9） mg/L]. ③The portal endotoxin of GLP-2 group [（82.8±6.3）, （90.1±7.8） Eu/L, P 〈 0.05] was lower than that in the traumatic group, but was similar to that in the control group [（78.9±5.4） Eu/L]. CONCLUSION： GLP-2 can improve the intestinal immunity of the rats following severe brain injury, thereby attenuating endotoxemia.