Abstract:

Objective  To explore the clinical changes of peripheral inflammatory markers and oxidative stress during post?acute and chronic phase after severe traumatic brain injury (sTBI).  Methods  A total of 24 sTBI patients were included in this study. The changes of peripheral inflammatory markers [interleukin (IL)-1β, IL-6, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α)] and oxidative stress parameters [glutathione peroxidase (GSH - Px), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and total plasma antioxidant activity (TEAA)] were monitored. Functional Independence Measure (FIM) and Dyskinesia Rating Scale (DRS) were used to evaluate cognitive function and motor function.  Results  There were significant differences on IL-6 (F = 105.982, P = 0.000), IFN-γ (F = 19.873, P = 0.000), GSH-Px (F = 162.090, P = 0.000), SOD (F = 28.254, P = 0.000) and CAT (F = 4.782, P = 0.011) during different periods of sTBI (post-acute phase, chronic early phase, chronic phase). IL-6 and GSH-Px in chronic early phase (IL-6: t = 11.753, P = 0.000; GSH-Px: t = 16.901, P = 0.000) and chronic phase (IL-6: t = 14.533, P = 0.000; GSH-Px: t = 13.828, P = 0.000) were significantly lower than post-acute phase. IL-6 and GSH-Px in chronic phase (IL-6: t = 2.341, P = 0.012; GSH-Px: t = 3.073, P = 0.003) were significantly lower than chronic early phase. SOD in chronic early phase and chronic phase was significantly higher than post-acute phase (t = 7.264, P = 0.000; t = 5.303, P = 0.000). CAT in chronic early phase was significantly higher than post-acute phase (t = 3.060, P = 0.003). After 12 months, 24 patients completed the follow-up, and their FIM scores were significantly increased (t = 36.260, P = 0.000), while DRS scores were significantly decreased (t = 49.010, P = 0.000). Pearson correlation analysis showed that IL-6 (r = 0.446, P = 0.020) and GSH-Px (r = 0.142, P = 0.000) were positively correlated with overall cognitive performance index (CPI). IL-6 was positively correlated with attention (r = 0.431, P = 0.026) and executive function (r = 0.522, P = 0.005) of synthetic index (SI). IFN-γ (r = 0.497, P = 0.009) and TNF-α (r = 0.479, P = 0.009) were positively correlated with executive function of SI. GSH-Px was positively correlated with all SI (r = 0.220, P = 0.000; r = 0.344, P = 0.000; r = 0.011, P = 0.000).  Conclusions  Imbalance of oxidative stress response and over-production of inflammatory markers in acute phase of patients with severe traumatic brain injury might adversely affect the neurological functional recovery. Inflammatory markers and oxidative stress response might offer a feasible way to monitor recovery and predict the prognosis after severe traumatic brain injury.

Key words: Brain injuries, Tumor necrosis factor-alpha, Oxidative stress

摘要：

目的 探讨重型颅脑创伤急性期和慢性期外周血炎症反应标志物和氧化应激参数表达变化。 方法 共24 例重型颅脑创伤患者测定炎症反应标志物［包括白细胞介素（IL）-1β、IL-6、干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）］和氧化应激参数［包括谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽还原酶（GR）和总血浆抗氧化剂活性（TEAA）］水平，采用功能独立性评价（FIM）和运动障碍评价量表（DRS）评价认知功能和运动功能。 结果 颅脑创伤患者不同时期（后急性期、慢性期早期、慢性期）IL-6（F = 105.982，P = 0.000）、IFN-γ（F = 19.873，P = 0.000）、GSH-Px（F = 162.090，P = 0.000）、SOD（F = 28.254，P = 0.000）和CAT（F = 4.782，P = 0.011）水平差异有统计学意义，其中，IL-6和GSH-Px水平慢性期早期（IL-6：t = 11.753，P = 0.000；GSH-Px：t = 16.901，P = 0.000）和慢性期（IL-6：t = 14.533，P = 0.000；GSH-Px：t = 13.828，P = 0.000）均低于后急性期，慢性期亦低于慢性期早期（IL-6：t = 2.341，P = 0.012；GSH-Px：t = 3.073，P = 0.003）；SOD 水平慢性期早期和慢性期高于后急性期（t =7.264，P = 0.000；t = 5.308，P = 0.000）；CAT 水平仅慢性期早期高于后急性期（t = 3.060，P = 0.003）。与随访初期相比，随访结束时FIM 评分升高（t = 36.260，P = 0.000）、DRS 评分降低（t = 49.010，P = 0.000）。Pearson 相关分析显示，IL?6（r = 0.446，P = 0.020）和GSH-Px（r = 0.142，P = 0.000）表达变化与全部认知功能指数呈正相关，IL-6 与认知功能综合指数之注意力（r = 0.431，P = 0.026）和执行功能（r = 0.522，P =0.005）呈正相关，IFN-γ（r = 0.497，P = 0.009）和TNF-α（r = 0.479，P = 0.009）仅与认知功能综合指数之执行功能呈正相关，GSH-Px 与认知功能综合指数均呈正相关（r = 0.220，P = 0.000；r = 0.344，P = 0.000；r =0.011，P = 0.000）。 结论 重型颅脑创伤患者急性期氧化应激平衡改变和炎症反应标志物过表达不利于功能恢复，测定炎症反应标志物和氧化应激参数表达变化，可以为重型颅脑创伤患者功能评价和预后预测提供一定依据。

关键词: 脑损伤, 肿瘤坏死因子α, 氧化性应激