亚低温联合依达拉奉对重型颅脑创伤患者脑脊液肿瘤坏死因子-α及白细胞介素-6表达的影响

Effects of mild hypothermia combined with edaravone on expressions of tumor necrosis factor-α and interleukin-6 in cerebrospinal fluid of patients with severe traumatic brain injury

目的：研究亚低温联合依达拉奉对重型颅脑创伤（sTBI）患者脑脊液肿瘤坏死因子-α（TNF-α）及白细胞介素-6（IL-6）表达及预后的影响。方法采用前瞻性随机对照研究方法，将武警后勤学院附属医院脑科中心收治的77例sTBI患者按随机数字表法分为对照组（38例）及治疗组（39例）。对照组给予脱水降颅压、营养脑神经、抗感染、呼吸机辅助呼吸及维持水电解质平衡等常规治疗，治疗组均于伤后24 h内在常规治疗基础上接受亚低温及依达拉奉治疗。采用放射免疫法测定两组患者不同时间点脑脊液TNF-α及IL-6含量，同时监测患者的颅内压（ICP）变化，并于伤后6个月根据格拉斯哥预后评分（GOS）判断预后。结果与对照组比较，伤后1 d治疗组患者脑脊液TNF-α及IL-6水平比较差异均无统计学意义（均P＞0.05），伤后3 d明显升高，7 d开始下降，14达谷值，且治疗组的降低程度较对照组更显著〔TNF-α（μg/L）：2.43±0.39比3.12±0.47，IL-6（ng/L）：83.53±11.48比101.69±13.64，均P＜0.01〕；两组治疗前ICP比较差异无统计学意义（P＞0.05），伤后1 d两组患者ICP逐渐升高，至伤后3 d达峰值，7 d开始下降，且以治疗组下降更显著〔mmHg（1 mmHg＝0.133 kPa）：14.88±3.73比21.76±4.78，P＜0.01〕。治疗组预后良好率较对照组明显升高〔35.9%（14/39）比21.1%（8/38），P＜0.05〕，病死率较对照组明显降低〔28.2%（11/39）比42.1%（16/38）， P＜0.05〕。结论亚低温联合依达拉奉可明显降低sTBI患者脑脊液TNF-α及IL-6表达水平，降低ICP，促进神经功能恢复，改善预后。

Objective To study the effect of mild hypothermia combined with edaravone on the expressions of tumor necrosis factor-α（TNF-α）and interleukin-6（IL-6）in cerebrospinal fluid（CSF）of patients with severe traumatic brain injury（sTBI）and on their prognoses. Methods A prospective randomizd controled trial was conducted. Seventy-seven patients in the Center for Neurology and Neurosurgery of Affiliated Hospital of Logistics University of Chinese People＆#39;s Armed Police Forces were randomly assigned into control group（38 cases）and treatment group（39 cases）according to random number table. All the patients were treated with routine treatments such as dehydration of intracranial pressure（ICP）,neural nutrition,anti-infection,mechanical ventilation and maintenance of water and electrolyte balance in control group,while in treatment group,the patients received mild hypothermia combined with edaravone on the basis of routine treatment within 24 hours after injury. The contents of TNF-αand IL-6 in CSF were measured by radio-immunoassay（RIA）at different time points in both groups. In the meantime,the ICP was also measured. The prognosis was evaluated after 6 months of injury according to Glasgow outcome scale（GOS）. Results Compared to control group,in the treatment group,the expression levels of TNF-αand IL-6 in CSF had no significant difference（both P〉0.05）on the 1st day after injury,but they were significantly increased on the 3rd day after injury,began to decline on the 7th day,and reached to the valley value on the 14th day after injury,the degree of descent in treatment group being more significant than that in control group〔TNF-α（μg/L）：2.43±0.39 vs. 3.12±0.47,IL-6（ng/L）：83.53±11.48 vs. 101.69±13.64,both P〈0.01〕. Before the treatment,the level of ICP in treatment group had no significant difference from that of control group（P〉0.05）,but it was gradually increased on the 1st day after injury in both groups,it reached the peak value on the 3rd day after injury,and began to decline on the 7th day after injury,the degree of descent being more significant in treatment group〔mmHg（1 mmHg=0.133 kPa）：14.88±3.73 vs. 21.76±4.78,P〈0.01〕. The favorable prognosis rate was significantly higher〔35.9%（14/39）vs. 21.1%（8/38）,P〈0.05〕,and the mortality was obviously lower in treatment group than those of control group〔28.2%（11）vs. 42.1%（16）,P〈0.05〕. Conclusion In patients with sTBI,mild hypothermia combined with edaravone can protect brain tissue through alleviating high ICP and decreasing the expression levels of TNF-αand IL-6 in CSF, resulting in promoting the recovery of nerve functions and improving prognosis.