脂氧素A4对脊髓缺血再灌注损伤模型大鼠的神经保护  

Lipoxanthin A4 plays a neuroprotective role against spinal cord ischemia-reperfusion injury in rats

作　　者：路坦[1] 常耀辉 尉娜[3] Lu Tan;Chang Yaohui;Wei Na(Department of Orthopedics,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China;Department of Orthopedics,Xiuwu County People’s Hospital,Jiaozuo 454350,Henan Province,China;Department of Neurology,the Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003,Henan Province,China)

机构地区：[1]新乡医学院第一附属医院骨外二科,河南省卫辉市453100 [2]修武县人民医院骨外科,河南省焦作市454350 [3]新乡医学院第三附属医院神经内二科,河南省新乡市453003

出　　处：《中国组织工程研究》2021年第26期4175-4179,共5页Chinese Journal of Tissue Engineering Research

基　　金：河南省高等学校重点科研项目(19A320003),项目负责人:路坦;新乡市科技攻关计划项目(CXGG17031),项目负责人:尉娜;新乡医学院第一附属医院青年基金项目(QN-2017-A002),项目负责人:路坦。

摘　　要：背景:前期研究已证明脂氧素A4对大鼠脊髓损伤具有神经保护作用,但其在脊髓缺血再灌注损伤中的作用机制仍不明确。目的:探讨脂氧素A4在大鼠脊髓缺血再灌注损伤中的保护作用。方法:将48只SD大鼠随机分为3组,每组16只:对照组、实验组制作脊髓缺血再灌注损伤模型,实验组脊髓鞘内注射脂氧素A4,对照组脊髓鞘内注射生理盐水;空白组不造模。造模后6,12,24,48 h,利用BBB评分评估大鼠运动神经功能;再灌注后24 h,采用Tunel法观察脊髓组织细胞凋亡情况,ELISA法检测脊髓组织Bcl-2和Bax浓度,Western blot检测脊髓组织cleaved-caspase-3、p-IKKβ和p-NF-κB蛋白的表达。实验通过新乡医学院第一附属医院伦理委员会批准(2018038)。结果与结论:①对照组不同时间点的BBB评分低于空白组(P<0.05),实验组造模后12,24,48 h的BBB评分高于对照组(P<0.05);②对照组细胞凋亡多于空白组(P<0.05),实验组少于对照组(P<0.05);③对照组脊髓组织内的Bcl-2、Bax水平均高于空白组(P<0.05);实验组的Bcl-2水平高于对照组(P<0.05),Bax水平低于对照组(P<0.05);④对照组cleaved-caspase-3、p-NF-κB蛋白表达强于空白组,p-IKKβ蛋白表达弱于空白组;实验组cleaved-caspase-3、p-NF-κB蛋白表达弱于对照组,p-IKKβ蛋白表达强于对照组;⑤结果表明,脂氧素A4可激活细胞质中caspase-3/IKKβ/NF-κB通道的活化,抑制细胞凋亡,起到治疗脊髓缺血再灌注损伤的作用。BACKGROUND:Previous studies have indicated that lipoxin A4 has a neuroprotective effect against spinal cord injury in rats,but its mechanism of action in spinal cord ischemia-reperfusion injury is still unclear.OBJECTIVE:To investigate the neuroprotective effect of lipoxin A4 in rats with spinal cord ischemia-reperfusion injury.METHODS:Forty-eight Sprague-Dawley rats were randomized into three groups(n=16 per group):Spinal cord ischemia-reperfusion injury models were built in control and experimental groups followed by intrathecal injection of normal saline and lipoxin A4 respectively,and no treatment was given in blank control group.Basso-Beattie-Bresnahan(BBB)score was used to evaluate motor nerve function in rats at 6,12,24,and 48 hours after modeling.At 24 hours after reperfusion,TUNEL assay was used to detect cell apoptosis in the rat spinal cord;ELISA was used to detect the levels of Bcl-2 and Bax in the rat spinal cord,and western blot assay was used to detect the levels of cleaved-caspase-3,p-IKKβand p-NF-κB proteins in the rat spinal cord.This experiment was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical University(approval No.2018038).RESULTS AND CONCLUSION:Compared with the blank control group,the BBB scores were lower in the control group at different observation time points(P<0.05),while compared with the control group,the BBB score was higher in the experimental group at 12,24,and 48 hours after modeling(P<0.05).There were more apoptotic cells in the control group than the blank control group(P<0.05),while the number of apoptotic cells in the experimental group was lower than that in the control group(P<0.05).The levels of Bcl-2 and Bax in the spinal cord were significantly higher in the control group than the blank control group,while compared with the control group,the experimental group showed a higher Bcl-2 level and a lower Bax level(P<0.05).Compared with the blank control group,the expressions of cleaved-caspase-3 and p-NF-κB proteins were strongly hig

关 键 词：组织构建 脊髓 脂氧素A4 脊髓缺血再灌注损伤 细胞凋亡 信号通路 

分 类 号：R459.9[医药卫生—治疗学] R-331[医药卫生—临床医学]