氧化应激在创伤性脑损伤后肠黏膜屏障损伤中的作用

摘要

目的:探讨氧化应激在创伤性脑损伤后肠黏膜屏障损伤中的作用.方法:雄性Wistar大鼠72只,随机分为3组,每组24只.A组为假手术组(对照组);B组为创伤性脑损伤组(TBI组),建立TBI模型;C组为二甲基亚砜预处理组(DMSO组),建立TBI前,使用DMSO预处理组.C组在制模前1 h皮下注射25%的二甲基亚砜(DMSO 4 μL/g),A组和B组则皮下注射同等量的生理盐水(4 μL/g).各组动物分别在手术后3、6、12、24 h处死(各时间点均为6只).动物处死后,取门静脉血测血清内毒素、DAO,取脑组织和回肠黏膜,观察组织形态学改变,并测定肠黏膜组织SOD、MDA、MPO、XOD含量.结果:肠黏膜受损后,TBI组血中内毒素含量明显增加(P < 0.05),DAO的活性3 h就明显升高,24 h升高程度最显著(P < 0.05);TBI组3 h肠黏膜组织中SOD活性已降低,24 h最为明显(P < 0.01);而MDA和MPO 3 h明显升高,24 h值最高(P < 0.01);XOD的含量3 h明显升高,6 h达最高后逐渐降低.DMSO组肠黏膜损伤明显减轻, 血中内毒素含量降低;血中DAO活性升高受抑(P < 0.05); SOD降低程度和MDA的升高程度明显受到抑制(P < 0.05),但仍高于正常(P < 0.05).结论:创伤性脑损伤后肠黏膜屏障的结构和功能受到损伤;氧化应激在创伤性脑损伤后肠黏膜屏障损伤过程中发挥了重要作用,XOD和激活的中性粒细胞是氧自由基的主要来源.%Objective: To observe the effect of oxidative stress on intestinal mucosal barrier dysfunction following traumatic brain injury (TBI). Methods: Seventy-two male Wistar rats were randomly divided into three groups, group B and group C served as TBI models, group A was designated as the normal control group(shame operation). In group C rats were treated with dimethyl sulfoxide(DMSO) prior to TBI, while rats in group A and B were treated with equivalent normal saline. During the experiment period, the morphological changes of intestinal mucosa were observed, and the intestinal mucosal permeability was detected by measuring the level of endotoxin, diamine oxidase(DAO). Superoxide dismutase(SOD), malondiadehycle (MDA), myeloperoxidase(MPO) and xanthine oxidase(XOD) activities were also detected. Results: During the observed period, the intestinal mucosal barrier function was damaged and the intestinal mucosal permeability increased. The content of endotoxin in serum significantly increased(P < 0.05). As early as 3 h after TBI, the DAO activity in the serum began to increase obviously. At 24 h after TBI it increased to the highest level(P < 0.05). In group TBI the activity of SOD in intestinal mucosal decreased significantly(P < 0.01); however the levels of MDA and the activity of MPO increased significantly (P < 0.01), the activity of XOD increased significantly as well, and then decreased after 6 h. When pr-treatment with DMSO, intestinal mucosal damage was improved, the content of endotoxin in serum was reduced (P < 0.05), and the increased DAO activity in the serum were inhibited (P < 0.05). When compared with group TBI, there was an inhibition in the decreased activity of SOD and the increased level of MDA in group DMSO (P < 0.05), but they were still higher than that of control group(P < 0.05). There were no significant differences in the activity of XOD and MPO between group DMSO and group TBI. Conclusion: The structure and function of intestinal mucosal barrier were damaged following TBI. Oxidative stress played an important role in the intestinal mucosal barrier dysfunction following TBI. Both XOD and activated polymorphonuclear neutrophils(PMN) were the major source of oxygen free radicals.