本文選題：丙戊酸 + 苯妥英��； 參考：《新鄉(xiāng)醫(yī)學(xué)院》2017年碩士論文

【摘要】：背景顱腦損傷(traumatic brain injury,TBI)是臨床上常見的一種外科疾病,具有發(fā)病率高、死亡率高、預(yù)后差等特點(diǎn)。TBI按損傷發(fā)生的前后可分為原發(fā)性及繼發(fā)性顱腦損傷。原發(fā)性顱腦損傷發(fā)生在損傷瞬間并立即產(chǎn)生相應(yīng)臨床癥狀。其治療相對(duì)困難。繼發(fā)性顱腦損傷于腦損傷后發(fā)生,主要涉及鈣超載、炎癥因子釋放、誘導(dǎo)神經(jīng)細(xì)胞不正常凋亡等過(guò)程。因此,其成為臨床醫(yī)師治療顱腦損傷一個(gè)重要的突破口�！吨匦惋B腦損傷診治指南(第四版)》提出:重型顱腦損傷(severe traumatic brain injury,sTBI)發(fā)生臨床外傷性癲癇的比率達(dá)12%,而使用腦電圖檢出亞臨床癲癇發(fā)作的患者比例高達(dá)20%-25%。因此,急性重型顱腦損傷(acute severe brain injury,ASBI)需常規(guī)給予藥物預(yù)防外傷性癲癇發(fā)生。目前,臨床上預(yù)防外傷性癲癇的一線藥物主要有苯妥英(phenytoin,PHT)、丙戊酸(valproic acid,VPA)等。丙戊酸鈉及苯妥英鈉作為臨床上兩種常用的抗癲癇藥,有效成分為VPA及PHT�！渡窠�(jīng)外科圍手術(shù)期和外傷后癲癇的預(yù)防及治療指南(草案)》推薦:VPA及PHT可常規(guī)應(yīng)用預(yù)防外傷性癲癇。臨床研究表明:應(yīng)用VPA與PHT預(yù)防外傷性癲癇后癲癇的總體發(fā)生率相似。近年來(lái)動(dòng)物模型實(shí)驗(yàn)研究表明,VPA在治療腦卒中、顱腦損傷、脊髓損傷等方面有顯著療效,具有抗炎、抗細(xì)胞凋亡和促進(jìn)神經(jīng)生長(zhǎng)等作用。Elizabeth通過(guò)顱腦損傷的臨床研究明確指出,PHT可有效預(yù)防外傷性癲癇,但對(duì)改善認(rèn)知功能障礙等神經(jīng)保護(hù)無(wú)統(tǒng)計(jì)學(xué)意義。目的觀察VPA對(duì)ASBI患者傷后14天內(nèi)血清中IL-6、NSE水平變化;觀察VPA對(duì)ASBI患者的神經(jīng)功能恢復(fù)的情況;探討VPA對(duì)ASBI的神經(jīng)保護(hù)作用。方法采用前瞻性隨機(jī)、對(duì)照試驗(yàn)方案,連續(xù)納入新鄉(xiāng)醫(yī)學(xué)院第一附屬醫(yī)院神經(jīng)外科2015年1月至2016年8月ASBI患者92例,其中2人治療期間不配合,2人治療期間死亡。最終入選病例總數(shù)為88例。入選患者分為觀察組(常規(guī)治療中應(yīng)用丙戊酸鈉,45例)和對(duì)照組(常規(guī)治療中應(yīng)用苯妥英鈉,43例);兩組患者均于顱腦損傷后第1、2、3、7、14d采集空腹靜脈血檢測(cè)血清NSE及IL-6水平;分別在治療前及治療后第7、14、21d對(duì)兩組患者進(jìn)行GCS評(píng)分;并在治療后1月及3月時(shí)進(jìn)行GOS評(píng)分;在治療后21天采用美國(guó)國(guó)立衛(wèi)生研究院卒中量表(National Institute of Health stroke scale,NIHSS)評(píng)分、Barthel指數(shù)評(píng)定兩組患者神經(jīng)功能恢復(fù)情況。結(jié)果兩組患者血清中的IL-6及NSE水平在損傷后第1d均迅速增加,IL-6水平在第2d達(dá)到最高峰,第3、7d的IL-6水平呈下降趨勢(shì),第14d的IL-6水平較7d有所上升;NSE水平在第2d達(dá)到第1個(gè)高峰,第3天呈下降趨勢(shì),第7d上升且達(dá)到第最高峰,第14d又呈下降趨勢(shì)。相同時(shí)刻IL-6、NSE水平均低于對(duì)照組。第1d無(wú)統(tǒng)計(jì)學(xué)差異,第2、3、7、14d差異有統(tǒng)計(jì)學(xué)意義;兩組患者治療后第7、14d時(shí)GCS評(píng)分無(wú)統(tǒng)計(jì)學(xué)差異(P0.05);治療后21d觀察組的GCS評(píng)分高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05);觀察組患者治療后1月及治療后3月時(shí)GOS評(píng)分明顯優(yōu)于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05);兩組患者治療前NIHSS評(píng)分、Barthel指數(shù)無(wú)統(tǒng)計(jì)學(xué)差異(P㧐0.05),治療后21d兩組患者NIHSS評(píng)分、Barthel指數(shù)較治療前均顯著改善(P0.05),且觀察組均較對(duì)照組改善明顯,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論VPA對(duì)ASBI患者神經(jīng)功能缺損具有改善作用,其機(jī)制可能與有效抑制IL-6引起的炎癥級(jí)聯(lián)反應(yīng),減少神經(jīng)細(xì)胞不正常凋亡而降低NSE有關(guān)。
[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.
【學(xué)位授予單位】：新鄉(xiāng)醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R651.15

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