大鼠颅脑损伤中肿瘤坏死因子-α及核转录因子-κB的变化及其意义

TNF-Alpha and NF-Kappa B Changes in Brain Tissue and Their Significance in Secondary Brain Injury of Rats

目的:通过观察肿瘤坏死因子(TNF-α)以及核转录因子κB(NF-κB)在颅脑损伤后脑组织中的表达变化,初步探讨两者在颅脑损伤后继发性脑损伤中的意义。方法:健康成年雄性SD大鼠64只,体重230-310g,随机分成对照组8只和颅脑损伤组56只,颅脑损伤组在外伤后1h、3h、6h、12h、24h、3d、7d处死,每组处死8只。取损伤灶周围的脑组织进行含水量以及超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)的测定,并进行病理切片观察其病理变化,最后用免疫组化法检测脑组织中TNF-α和NF-κB的含量。结果:1成功构建大鼠颅脑损伤的模型,颅脑损伤后的各时间点神经功能评分差异无统计学意义(P>0.05);2颅脑损伤组大鼠的脑组织含水量较对照组显著升高,并且在3d达到高峰,7d时逐渐下降,但仍高于对照组,差异有统计学意义(P<0.05);3大鼠颅脑损伤后切片表现为有大量的炎症细胞积聚,并有不同程度的脑细胞水肿,随着时间的推移逐渐加重,在第7d时,水肿较之前减轻,但仍有大量的炎性细胞浸润以及少量的纤维组织增生;4大鼠颅脑损伤后1h开始,损伤灶周围的脑组织中MDA的含量显著升高,且在之后的时间内持续升高,在3d时达到高峰,随后下降,7d时表达仍然高于对照组,而损伤组的SOD活性及GSH的活力明显降低,在7d时仍低于对照组,差异有统计学意义(P<0.05);5TNF-α以及NF-κB在颅脑损伤组中含量显著高于对照组,且在颅脑损伤后1h开始升高,在3d左右达到高峰,7d时稍有降低,但仍高于对照组,为高表达状态。结论:颅脑损伤后TNF-α以及NF-κB的变化趋势与继发性脑损伤的临床表现一致,参与了继发性脑损伤的病理过程。

Objective：To explore the relationship between TNF-αand NF-κB in brain injury,as well as its potential mechanisms.Methods：A total of 64 adult healthy male rats were divided into control group（n=8）and brain injury group（n=56）.Brain injury model was induced by using improved Feeney method.The brain injury group was divided into seven subgroups by different sacrificed time after injury as 1h,3h,6h,12 h,24h,3d,and 7d,with 8rats in each subgroup.The water content,the superoxide dismutase（SOD）,malonic aldehyde（MDA）,and glutathione（GSH）in peri-contusion brain tissue were measured.HE staining and immunohistochemical methods were adopted to detect the expression of NF-κB and TNF-αlevels in brain tissue.Results：The model of brain injury was successfully constructed.The water content in brain of brain injury group is significantly higher,and peaked at the third day,decreased by the 7th day,but was still in higher than in control group（P〈0.05）.Inflammatory changes were gradually increased after injury.MDA in brain injury group is significantly higher,peaked at the third day,and then decreased by the 7th day,but was still higher than in control group.SOD activity and GSH level in brain injury group were significantly lower,and increased by the 7th day,but were still lower than in control group（P〈0.05）.TNF-αand NF-κB in brain injury group were significantly higher,and peaked at the third day,decreased by 7th day,but were still higher than in control group（P〈0.05）.Conclusion：The expression of TNF-ɑand NF-κB are consistent with the clinical manifestations of brain injury,and their changes may involved in the pathogenesis of secondary brain injury.