丙戊酸对急性重型颅脑损伤患者的神经保护作用

发布时间：2018-06-30 17:02

本文选题：丙戊酸 + 苯妥英　；参考：《新乡医学院》2017年硕士论文

【摘要】：背景颅脑损伤(traumatic brain injury,TBI)是临床上常见的一种外科疾病,具有发病率高、死亡率高、预后差等特点。TBI按损伤发生的前后可分为原发性及继发性颅脑损伤。原发性颅脑损伤发生在损伤瞬间并立即产生相应临床症状。其治疗相对困难。继发性颅脑损伤于脑损伤后发生,主要涉及钙超载、炎症因子释放、诱导神经细胞不正常凋亡等过程。因此,其成为临床医师治疗颅脑损伤一个重要的突破口。《重型颅脑损伤诊治指南(第四版)》提出:重型颅脑损伤(severe traumatic brain injury,sTBI)发生临床外伤性癫痫的比率达12%,而使用脑电图检出亚临床癫痫发作的患者比例高达20%-25%。因此,急性重型颅脑损伤(acute severe brain injury,ASBI)需常规给予药物预防外伤性癫痫发生。目前,临床上预防外伤性癫痫的一线药物主要有苯妥英(phenytoin,PHT)、丙戊酸(valproic acid,VPA)等。丙戊酸钠及苯妥英钠作为临床上两种常用的抗癫痫药,有效成分为VPA及PHT。《神经外科围手术期和外伤后癫痫的预防及治疗指南(草案)》推荐:VPA及PHT可常规应用预防外伤性癫痫。临床研究表明:应用VPA与PHT预防外伤性癫痫后癫痫的总体发生率相似。近年来动物模型实验研究表明,VPA在治疗脑卒中、颅脑损伤、脊髓损伤等方面有显著疗效,具有抗炎、抗细胞凋亡和促进神经生长等作用。Elizabeth通过颅脑损伤的临床研究明确指出,PHT可有效预防外伤性癫痫,但对改善认知功能障碍等神经保护无统计学意义。目的观察VPA对ASBI患者伤后14天内血清中IL-6、NSE水平变化;观察VPA对ASBI患者的神经功能恢复的情况;探讨VPA对ASBI的神经保护作用。方法采用前瞻性随机、对照试验方案,连续纳入新乡医学院第一附属医院神经外科2015年1月至2016年8月ASBI患者92例,其中2人治疗期间不配合,2人治疗期间死亡。最终入选病例总数为88例。入选患者分为观察组(常规治疗中应用丙戊酸钠,45例)和对照组(常规治疗中应用苯妥英钠,43例);两组患者均于颅脑损伤后第1、2、3、7、14d采集空腹静脉血检测血清NSE及IL-6水平;分别在治疗前及治疗后第7、14、21d对两组患者进行GCS评分;并在治疗后1月及3月时进行GOS评分;在治疗后21天采用美国国立卫生研究院卒中量表(National Institute of Health stroke scale,NIHSS)评分、Barthel指数评定两组患者神经功能恢复情况。结果两组患者血清中的IL-6及NSE水平在损伤后第1d均迅速增加,IL-6水平在第2d达到最高峰,第3、7d的IL-6水平呈下降趋势,第14d的IL-6水平较7d有所上升;NSE水平在第2d达到第1个高峰,第3天呈下降趋势,第7d上升且达到第最高峰,第14d又呈下降趋势。相同时刻IL-6、NSE水平均低于对照组。第1d无统计学差异,第2、3、7、14d差异有统计学意义;两组患者治疗后第7、14d时GCS评分无统计学差异(P0.05);治疗后21d观察组的GCS评分高于对照组,差异有统计学意义(P0.05);观察组患者治疗后1月及治疗后3月时GOS评分明显优于对照组,差异有统计学意义(P0.05);两组患者治疗前NIHSS评分、Barthel指数无统计学差异(P㧐0.05),治疗后21d两组患者NIHSS评分、Barthel指数较治疗前均显著改善(P0.05),且观察组均较对照组改善明显,差异有统计学意义(P0.05)。结论VPA对ASBI患者神经功能缺损具有改善作用,其机制可能与有效抑制IL-6引起的炎症级联反应,减少神经细胞不正常凋亡而降低NSE有关。
[Abstract]:Traumatic brain injury (TBI) is a common surgical disease with high morbidity, high mortality and poor prognosis..TBI can be divided into primary and secondary craniocerebral injury before and after injury. Primary craniocerebral injury occurs at the moment of injury and produces corresponding clinical symptoms. Secondary craniocerebral injury occurred after brain injury, which mainly involved calcium overload, inflammatory factors release, and induced abnormal apoptosis of nerve cells. Therefore, it became an important breakthrough for clinicians to treat craniocerebral injury. < severe traumatic brain in > severe craniocerebral injury (severe craniocerebral injury) guide (EDITION): severe craniocerebral injury (brain in) Jury, sTBI) the incidence of clinical traumatic epilepsy is 12%, and the proportion of patients with subclinical epileptic seizures using electroencephalogram is as high as 20%-25%., so acute severe craniocerebral injury (acute severe brain injury, ASBI) needs to be routinely given drugs to prevent traumatic epilepsy. Phenytoin (PHT), valproic acid (valproic acid, VPA), sodium valproate and phenytoin sodium as two commonly used antiepileptic drugs, effective ingredients are the guidelines for the prevention and treatment of epilepsy in the perioperative and post traumatic epilepsy of VPA and PHT.< Department of Neurosurgery (Draft): VPA and PHT can be used to prevent traumatic epilepsy. Clinical study table The general incidence of VPA and PHT in the prevention of epilepsy after traumatic epilepsy is similar. In recent years, animal model experiments have shown that VPA has significant effect in the treatment of stroke, brain injury, spinal cord injury and so on. The clinical study of anti-inflammatory, anti apoptosis and promoting nerve growth by using.Elizabeth through brain injury is clearly pointed out. PHT can effectively prevent traumatic epilepsy, but it has no statistical significance for improving cognitive impairment. Objective To observe the changes of serum IL-6 and NSE levels in patients with ASBI after 14 days after injury, and to observe the neurological function of VPA in ASBI patients and to explore the neuroprotective effect of VPA on ASBI. Methods a prospective randomized, controlled trial was used. 92 cases of ASBI patients were included in First Affiliated Hospital of Xinxiang Medical College Department of neurosurgery from January 2015 to August 2016. 2 of them were not matched during the treatment period and 2 people died during the treatment period. The total number of final selected cases was 88. The selected patients were divided into the observation group (conventional treatment with valproate, 45 cases) and the control group (routine treatment). Phenytoin sodium, 43 cases); two groups were collected in 1,2,3,7,14d after craniocerebral injury to collect serum NSE and IL-6 levels by fasting venous blood test. Before and after treatment, two groups of patients were evaluated with GCS, and the GOS scores were carried out in January and March after treatment, and the National Institutes of Health Stroke scale (Na) was used 21 days after treatment (Na Tional Institute of Health stroke scale, NIHSS) score and Barthel index were used to evaluate the recovery of nerve function in two groups of patients. Results the level of IL-6 and NSE in the serum of the two groups increased rapidly after the injury, and the IL-6 level reached the highest peak. The level in 2D reached first peaks, the third days showed a downward trend, the 7d increased and reached the highest peak, and the 14d showed a downward trend. The same time IL-6, NSE level were lower than the control group. There was no statistical difference in 1D, 2,3,7,14d difference was statistically significant; there was no statistical difference in the GCS score of the two groups after treatment (P0.05); 21 after treatment, after treatment, the difference was not statistically significant (P0.05). After treatment, 21 The GCS score of the D observation group was higher than that of the control group (P0.05); the GOS scores of the patients in the observation group were significantly better than those in the control group after the treatment in January and the March after the treatment. The difference was statistically significant (P0.05); there was no statistical difference between the two groups before treatment, the Barthel index was no statistical difference (P? 0.05), and the NIHSS score of the patients in the 21d two groups after treatment, Barthel finger. Compared with the control group, the number of VPA was significantly improved compared with the control group (P0.05). Conclusion VPA could improve the neural function defect in ASBI patients. The mechanism may be related to the effective inhibition of IL-6 induced inflammatory cascade, reducing the abnormal apoptosis of nerve cells and reducing NSE.
【学位授予单位】：新乡医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R651.15

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