利多卡因对大鼠蛛网膜下腔出血后迟发性脑血管痉挛的影响及脑保护作用机制研究  

Effects of lidocaine on delayed cerebral vasospasm and cerebral protection in rats after subarachnoid hemorrhage

作　　者：苏飞[1] 陈博文 李向男 刘佳琦 陈扬 Su Fei;Chen Bowen;Li Xiangnan;Liu Jiaqi;Chen Yang(Department of Neurosurgery,Baoding First Central Hospital,Hebei Province,Baoding 071000,China;不详)

机构地区：[1]河北省保定市第一中心医院神经外三科,071000 [2]河北省保定市第一中心医院神经重症医学科,071000 [3]华北理工大学附属医院神经外二科,唐山063000

出　　处：《疑难病杂志》2021年第12期1252-1256,1262,共6页Chinese Journal of Difficult and Complicated Cases

基　　金：保定市科学技术研究与发展指导计划项目(18ZF114)。

摘　　要：目的观察利多卡因对大鼠蛛网膜下腔出血(SAH)后迟发性脑血管痉挛(CVS)的影响及脑保护作用机制。方法实验于2019年2-5月于华北理工大学附属医院神经外科实验室进行。将54只大鼠按随机数字表法分为假手术组、SAH组和利多卡因组(2%利多卡因0.1 ml,经枕大池注入)各18只,采用枕大池注血法复制SAH模型。分别在造模后3 d、5 d和7 d,观察脑组织病理变化和凋亡情况,测量基底动脉管径周长和管壁厚度。造模后7 d,试剂盒测定脑脊液超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、内皮素-1(ET-1)和一氧化氮(NO)水平,Western Blot测定脑组织中p-p38MAPK/p38MAPK和p-eNOS/eNOS蛋白表达。结果利多卡因注射后第3d、5d和7d,SAH组大鼠基底动脉内径周长均小于假手术组,基底动脉壁厚度和海马组织细胞凋亡率高于假手术组(P<0.05);利多卡因组基底动脉内径周长大于SAH组,基底动脉壁厚度和海马组织细胞凋亡率低于SAH组(P<0.05)。利多卡因注射后第7d,SAH组大鼠脑脊液SOD、GSH-Px和NO水平低于假手术组,MDA和ET-1水平高于假手术组,脑组织p-p38MAPK/p38MAPK蛋白表达高于假手术组,p-eNOS/eNOS蛋白表达低于假手术组(P<0.05);利多卡因组脑脊液SOD、GSH-Px和NO水平高于SAH组,MDA和ET-1水平低于SAH组,脑组织p-p38MAPK/p38MAPK蛋白表达低于SAH组,p-eNOS/eNOS蛋白表达高于SAH组(P<0.05)。结论利多卡因可能通过抑制p38MAPK/eNOS的磷酸化,调节血管收缩因子表达,抑制SAH大鼠CVS的发生,减轻脑组织损伤。Objective To observe the effects of lidocaine on delayed cerebral vasospasm(CVS)and cerebral protection in rats after subarachnoid hemorrhage(SAH).Methods The experiment was conducted in the Laboratory of Neurosurgery,Affiliated Hospital of North China University of Science and Technology from February to May 2019.A total of 54 rats were randomly divided into sham operation group,SAH group and lidocaine group(injection of 0.1 ml 2%lidocaine at cisterna magna),18 rats in each group.SAH models were replicated by cisternus magna injection.At 3d,5d,and 7d after lidocaine injection,pathological changes and apoptosis of cerebral tissues were observed.The circumference and thickness of basilar artery were measured.At 7d after lidocaine injection,levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA),endothelin-1(ET-1)and nitric oxide(NO)in cerebrospinal fluid(CSF)were detected by kits.The expression of p-p38MAPK/p38MAPK and p-eNOS/eNOS proteins in cerebral tissue were detected by Western Blot.Results At 3 d,5 d and 7d after lidocaine injection,circumference of basilar artery in SAH group was shorter than that in sham operation group,while thickness of basilar artery wall and apoptosis rate of hippocampal tissues were higher than those in sham operation group(P<0.05).The circumference of basilar artery in lidocaine group was longer than that in SAH group,while thickness of basilar artery wall and apoptosis rate of hippocampal tissues were lower than those in SAH group(P<0.05).At 7d after lidocaine injection,levels of SOD,GSH-Px and NO in CSF of SAH group were lower than those of sham operation group,levels of MDA and ET-1 were higher than those of sham operation group,expression of p-p38MAPK/p38MAPK in cerebral tissues was higher than that of sham operation group,and expression of p-eNOS/eNOS was lower than that of sham operation group(P<0.05).The levels of SOD,GSH-Px and NO in CSF of lidocaine group were higher than those of SAH group,levels of MDA and ET-1 were lower than those of SAH g

关 键 词：蛛网膜下腔出血 脑血管痉挛 利多卡因 一氧化氮 内皮素-1 大鼠 

分 类 号：R743.35[医药卫生—神经病学与精神病学]