目的探讨载脂蛋白Z(apoE)拟肽COGl410对创伤性脑损伤(TBI)急性期脑组织肿瘤坏死因子-α(TNF—α)和脑水肿的影响。方法雄性C57BL/6J基因野生鼠45只按随机数字表法分为假手术组、等渗盐水组、apoE拟肽干预组,每组15只。后2组小鼠采用控制性气压冲击法构建TBI模型,模型制作完成30min后分别予以尾静脉注射200μL等渗盐水和apoE拟肽COG1410(0.2mg/mL)。造模后24h,RT—PCR、酶联免疫吸附实验(ELISA)法分别检测小鼠伤侧半脑TNF—α mRNA的表达和TNF-α的含量;MRI T2WI像扫描检测小鼠脑水肿体积及双侧侧脑室体积比。结果RT-PCR、ELISA检测显示:与假手术组比较,等渗盐水组、apoE拟肽干预组小鼠脑组织TNF-α mRNA和含量明显升高,且apoE拟肽干预组小鼠脑组织TNF-α mRNA和含量较等渗盐水组明显降低,差异均有统计学意义(P〈0.05)。MRI T2WI脑扫描显示apoE拟肽干预组小鼠脑水肿体积较等渗盐水组明显降低,差异有统计学意义(P〈0.05);与假手术组比较,等渗盐水组、apoE拟肽干预组小鼠伤侧/对侧侧脑室体积比降低,且apoE拟肽干预组小鼠伤侧/对侧侧脑室体积比较等渗盐水组明显升高,差异有统计学意义(P〈0.05)。相关性分析显示等渗盐水组与apoE拟肽干预组小鼠TBI急性期脑组织TNF-α含量和脑水肿体积呈正相关性(r=0.969,P=0.001)。结论apoE拟肽可通过抑制TBI急性期脑组织TNF-α的过度表达从而抑制血管源性脑水肿。
Objective To investigate the effect of apolipoprotein E (apoE) peptide on tumor necrosis factor-ct (TNF-tx) and brain edema after traumatic brain injury (TBI) at the acute stage. Methods A total of 45 C57BL/6J male wild type mice were divided into three parallel groups, namely sham-operated group, normal saline group and apoE intervention group (n=15). The mice TB1 models in the later two groups were constructed by controlled cortex impact devices; the mice in the apoE intervention group received 200 μL apoE peptide-COG1410 (0.2 mg/mL) through tail vein within 30 min after injury and the mice in the normal saline group received 200 μL isotonic saline. Twenty-four h after injury, real time-PCR and ELISA were used to detect the TNF-α mRNA expression and TNF-α content; and, and MR T2-weighted imaging was employed to detect the volume of brain edema and the lateral ventricles. Results The TNF-α mRNA expression and TNF-α content in the normal saline group and apoE intervention group were significantly increased as compared with those in the sham-operated group (P〈0.05); the difference between normal saline group and apoE intervention group was significant (P〈0.05). As compared with that in the sham-operated group, the rate of ipsilateral lateral ventricle of injury/the opposite one in the normal saline group and apoE intervention group were significantly decreased (P〈0.05), and that in the apoE intervention group was significantly increased as compared with that in the normal saline group (P〈0.05), which meant that the ipsilateral lateral ventricle of the injury was pushed by the swollen brain tissues. Correlation analysis indicated that TNF-α content in the brain tissues at acute stage of TBI was positively correlated to the cerebral edema volume (r=0.969, P=0.001). Conclusion ApoE peptide could reduce TNF-α expression and vasogenic cerebral edema after TBI at the acute stage.