维生素C在急性大剂量乙醇摄入后颅脑损伤中作用的研究

目的探讨维生素C（VitC）在急性大剂量乙醇摄入后颅脑损伤（TBI）后继发性脑损伤的作用及其可能机制。 方法将实验大鼠随机分为打击+生理盐水组（TBI+only）；打击+乙醇+生理盐水组（TBI+EtOH）；打击+VitC组（TBI+VitC）；打击+乙醇+VitC组（TBI+EtOH+VitC），每组10只。建立中度TBI模型，TBI后24 h进行神经功能损伤评分、脑含水量及伊文氏蓝含量测定；采用Western blot法测定TBI后24 h的损伤侧脑组织中细胞色素P450（CYP2E1），水通道蛋白-4（AQP-4），基质金属蛋白酶-9（MMP-9）和血脑屏障紧密连结蛋白（Occludin）的表达情况。 结果打击24 h后，TBI+EtOH组的神经功能损伤评分、脑含水量和伊文氏蓝含量明显增加，VitC干预后，各项指标明显减少，组间差异有统计学意义（P<0.05）；与TBI+EtOH组相比，TBI+EtOH+VitC组的CYP2E1表达减少，AQP-4和MMP-9的含量降低，Occludin的含量增高，组间差异有统计学意义（P<0.05）。 结论急性乙醇摄入加剧了TBI后细胞毒性脑水肿，而VitC可通过CYP2E1减少AQP-4和MMP-9的激活，增加Occludin蛋白的表达，减少血脑屏障紧密连接的分解及完整性的破坏，降低血脑屏障的开放并减轻脑水肿，最终改善神经功能。

Effect of vitamin C for the pre-injury high ethanol intake in rats following traumatic brain injury

ObjectiveTo investigate the effect of vitamin C (VitC) on reducing secondary brain injury caused by traumatic brain injury (TBI) after alcohol consumption and its possible mechanism. MethodsRats were randomly assigned into TBI+only group, TBI+EtOH group, TBI+VitC group and TBI+EtOH+VitC group, 10 rats in each group. TBI model was established, and 24 h after TBI, the neurological injury score, brain water content and Evans blue content were measured. Western blot was used to evaluate the expressions of P450 (CYP2E1), AQP-4, MMP-9 and Occludin in the tissue of the damaged brain 24 h after TBI with alcohol consumption. ResultsAfter 24 h of percussion, the neurological injury score, brain water content and Evans blue content of TBI+EtOH group were significantly increased, after VitC intervention, the indexes were significantly reduced, the difference among the groups was statistically significant (P<0.05); compared with TBI+EtOH group, the expression of CYP2E1, AQP-4 and MMP-9 were decreased, the content of occludin was increased, and the difference between the groups was statistically significant (P<0.05). ConclusionAcute ethanol intake aggravates cytotoxic brain edema after TBI, while VitC can reduce the activation of AQP-4 and MMP-9 through CYP2E1, increase the expression of occludin protein, reduce the breakdown of tight connection of blood-brain barrier and the destruction of integrity, reduce the opening of blood-brain barrier and reduce brain edema, and ultimately improve neurological function.