丙泊酚对创伤性脑损伤后大鼠神经功能的保护作用及其相关机制  

Protective effect of propofol on neurological function in rats after traumatic brain injury and related mechanism

作　　者：方仲宁 陈祥荣[1] 陈峻严[1] 邬树凯[1] 卢明智 Fang Zhongning;Chen Xiangrong;Chen Junyan;Wu Shukai;Lu Mingzhi(Department of Neurosurgery, Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China)

机构地区：[1]福建医科大学附属第二医院神经外科,泉州362000

出　　处：《中华创伤杂志》2019年第10期936-941,共6页Chinese Journal of Trauma

基　　金：福建省科技创新联合资金项目(2017Y9084).

摘　　要：目的探讨丙泊酚对创伤性脑损伤(TBI)后大鼠神经功能的保护作用及其可能机制。方法选取96只SD大鼠,采用改良Feeney法制备TBI模型。按随机数字表法分为假手术组、假手术+丙泊酚组、TBI组和TBI+丙泊酚组,每组24只。假手术+丙泊酚组和TBI+丙泊酚组给予丙泊酚50 mg/kg,1次/d。假手术组、TBI组注射等量生理盐水。分别于伤后1,3,7,14 d进行改良神经功能缺损评分(mNSS),干-湿比重法检测损伤区脑皮质脑含水量,TUNEL染色检测神经细胞凋亡数,化学荧光法检测活性氧簇(ROS)含量,采用Western blot法测定肌醇需求酶1(IRE-1)、增强子结合蛋白同源蛋白(CHOP)、血红素加氧酶1(HO-1)、醌氧化还原酶1(NQO1)和核因子E2相关因子2(Nrf2)蛋白的表达。结果与假手术组、假手术+丙泊酚组比较,TBI组和TBI+丙泊酚组伤后1,3,7,14 d mNSS、脑组织含水量、细胞凋亡数、ROS含量升高(P<0.05);与TBI组比较,TBI+丙泊酚组mNSS伤后7 d明显降低[(9.3±1.4)分∶(10.9±1.2)分](P<0.05),脑组织含水量伤后3 d明显降低[(81.0±0.8)%∶(82.1±0.8)%](P<0.05),细胞凋亡数伤后7 d明显减少[(14.1±1.4)%∶(15.6±1.6)%]且伤后14 d减少最为显著[(10.4±1.5)%∶(13.2±1.4)%](P均<0.05),ROS含量伤后7 d明显降低[(61.5±4.0)RFU ∶(77.3±5.5)RFU](P<0.05)。与假手术组和假手术+丙泊酚组比较,TBI组和TBI+丙泊酚组IRE-1、CHOP表达显著升高(P<0.05),TBI组HO-1、NQO1和Nrf2表达明显降低(P<0.05), TBI+丙泊酚组HO-1和NQO1表达升高(P<0.05),而Nrf2的表达稍降低(P<0.05)。与TBI组比较,TBI+丙泊酚组IRE-1、CHOP表达降低(P<0.05),同时HO-1、NQO1和Nrf2表达明显升高(P<0.05)。结论大鼠TBI后,丙泊酚能够通过激活Nrf2-抗氧化反应原件通路,减轻氧化应激反应和脑水肿,抑制神经细胞凋亡,起到神经保护作用。Objective To investigate the protective effect of propofol on neurological function in rats after traumatic brain injury (TBI) and its possible mechanism. Methods A total of 96 SD rats were randomly divided into sham operation group, sham operation+ propofol group, TBI group and TBI + propofol group, with 24 rats in each group. The TBI model was prepared by modified Feeney method. The sham operation+ propofol group and the TBI+ propofol group were given 50 mg/kg of propofol once daily. The sham operation group and the TBI group were injected with the same amount of normal saline. Modified neurobehavioral functional scores (mNSS) were evaluated at 1, 3, 7 and 14 days after injury;dry-wet specific gravity method was used to detect brain water content in injured area;TUNEL staining was used to detect neuronal apoptosis;chemiluminescence was used to detect activity of Oxygen cluster (ROS) content;Western blot was used to determine the expressions of inositol requirement enzyme 1 (IRE-1), enhancer binding protein homolog protein (CHOP), heme oxygenase 1 (HO-1), quinone oxidoreductase 1 (NQO1) and nuclear factor E2 related factor 2 (Nrf2) protein. Results Compared with the sham operation group and the sham operation + propofol group, the mNSS, brain tissue water content, apoptosis number and ROS increased at 1, 3, 7 and 14 days after TBI in the TBI group and TBI + propofol group (P<0.05). Compared with TBI group, mNSS in TBI+ propofol group decreased significantly [(9.3±1.4)points ∶(10.9±1.2)points] 7 days after injury (P<0.05);the brain tissue water content decreased significantly [(81.0±0.8)%∶(82.1±0.8)%] 3 days after injury (P<0.05);the number of apoptotic cells decreased significantly 7 days after injury[(14.1±1.4)%∶(15.6±1.6)%], with the most significant decrease at 14 days after injury [( 10.4±1.5)%∶(13.2±1.4)%(P<0.05);and ROS decreased significantly 7 days after injury [(61.5±4.0)RFU∶(77.3±5.5)RFU](P<0.05). Compared with the sham operation group and the sham operation+ propofol group, the exp

关 键 词：脑损伤 氧化应激 核因子E2相关因子2 

分 类 号：R651.15[医药卫生—外科学]