奥希替尼治疗大鼠脊髓损伤的时间窗研究  

The time window of osimertinib in the treatment of spinal cord injury in rats

作　　者：李在望 武晶晶 王倩 涂景梅[1] 韩晶 LI Zaiwang;WU Jingjing;WANG Qian(Department of Neurology,Shenzhen People’s Hospital(Second Clinical Medical College of Ji’nan University,First Affiliated Hospital of Southern University of Science and Technology),Shenzhen 518020,Chiana)

机构地区：[1]暨南大学第二临床医学院,南方科技大学第一附属医院深圳市人民医院神经内科,广东深圳518020 [2]盐城市第一人民医院神经内科,江苏盐城224001

出　　处：《中风与神经疾病杂志》2021年第2期100-104,共5页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金项目(No.81671219、82071364);深圳市自然科学基金项目(JCYJ20190806145812589)。

摘　　要：目的明确表皮生长因子(epidermal growth factor receptor,EGFR)抑制剂奥希替尼治疗脊髓损伤(spinal cord injury,SCI)的最佳时机。方法将60只大鼠随机分为6组(每组10只):损伤对照组(injury组)和5个奥希替尼治疗组:0天组(0 d组)、1天组(1 d组)、3天组(3 d组)、5天组(5 d组)、7天组(7 d组)。建立大鼠脊髓损伤模型后,奥希替尼治疗组分别于术后即刻、术后1 d、3 d、5 d、7 d给予奥希替尼进行干预,损伤对照组使用溶剂(生理盐水)作为对照。应用BBB评分量表于术后1 d及术后每周评估各组大鼠行为学的改变,每天记录各组残余尿量;术后14 d,各组随机选择5只大鼠处死,取脊髓组织,应用Western blot技术检测GAP-43的表达。结果(1)0 d组、1 d组和3 d组大鼠的后肢运动功能评分(BBB评分)明显优于5 d组、7 d组和injury组(P<0.05),0 d组、1 d组和3 d组无明显差异(P>0.05);(2)0 d组、1 d组和3 d组大鼠残余尿量明显少于其他各组(均P<0.05),0 d组、1 d组和3 d组无明显差异(P>0.05);(3)大鼠脊髓损伤后14 d,0 d组、1 d组和3 d组的GAP-43表达量明显高于其他各组(分别P<0.05,P<0.01),0 d组、1 d组和3 d组无明显差异(P>0.05)。结论EGFR抑制剂奥希替尼治疗大鼠脊髓损伤的最佳时机是脊髓损伤后0 h~72 h。Objective To determine the optimal time window to treat spinal cord injury(SCI)by epidermal growth factor receptor(EGFR)inhibitor osimertinib.Methods 60 rats were randomly divided into 6 groups(10 in each group):injury control group and 5 osimertinib-treated groups(0 d,1 d,3 d,5 d and 7 d group).After rats spinal cord injury model was established,the rats in osimertinib-treated group were applied with at different time(0 day,1 day,3 days and 7 days)after injury,while the injury group animals were only given vehicle solution(normal saline)lacking osimertinib.Neurological deficits was evaluated by using the BBB locomotor scale at first day and weekly post-injury.Residual urine volume was recorded everyday in each group.14 days after SCI,5 rats were randomly selected and sacrificed.Spinal cord tissues were collected,and the expression of GAP-43 was detected by Western blot.Results(1)The BBB score of rats in 0 d group,1 d group,3 d group was significantly higher than 5 d group,7 d group and injury groups(P<0.05),and there was no significant difference among 0 d group,1 d group and 3 d group(P>0.05).(2)The residual urine volume of rats in 0 d group,1 d group,3 d group was significantly less than that other groups(P<0.05),and there was no significant difference among 0 d group,1 d group and 3 d group(P>0.05).(3)The expression of GAP-43 in 0 d group,1 d group and 3 d group was significantly higher than other groups(P<0.05,or P<0.01),and there was no significant difference among 0 d group,1 d group and 3 d group(P>0.05).Conclusion The optimal time of EGFR inhibitor osimertinib to treat spinal cord injury in rats was 0 h to 72 h after spinal cord injury.

关 键 词：脊髓损伤 表皮生长因子受体 奥希替尼 BBB评分 生长相关蛋白43 

分 类 号：R744[医药卫生—神经病学与精神病学]