摘要
目的研究表皮生长因子受体(EGFR)抑制剂奥希替尼对大鼠脊髓损伤(spinal cord injury,SCI)后致炎因子、紧密连接蛋白表达及神经功能的影响。方法将60只SD大鼠随机分为:假手术组、损伤组、奥希替尼组,建立大鼠脊髓损伤模型。造模后3、7 d采用Western blot检测各组大鼠脊髓组织紧密连接蛋白ZO-1、Occludin和致炎因子IL-1β、TNF-α、COX-2、iNOS以及p-EGFR、EGFR蛋白的表达;造模后7 d应用免疫荧光染色及Western blot技术检测各组大鼠脊髓组织GFAP、CD11b的表达;应用Luxol Fast Blue染色评估各组大鼠髄鞘脱失情况,应用BBB评分量表评估大鼠运动功能,应用膀胱残余尿量评估大鼠排尿功能。结果(1)SCI后3、7 d,奥希替尼组致炎因子IL-1β、TNF-α、COX-2、iNOS表达量明显低于损伤组(均P<0.05);(2)SCI后3、7 d,奥希替尼组紧密连接蛋白ZO-1、Occludin蛋白表达量明显高于损伤组(均P<0.05);(3)SCI后3、7 d,奥希替尼组EGFR活化较损伤组减少(均P<0.05);(4)SCI后7 d损伤组GFAP及CD11b表达均明显增加,而奥希替尼组两者表达均较损伤组明显减少(均P<0.05);(5)与损伤组比较,奥希替尼组脊髓组织髄鞘脱失面积明显减少(P<0.05),BBB评分明显升高(P<0.05),残余尿量明显减少(P<0.05)。结论EGFR抑制剂奥希替尼可有效抑制SCI后EGFR活化,降低脊髓组织致炎因子表达,减少紧密连接蛋白缺失,抑制胶质细胞活化,缓解髄鞘脱失,促进神经功能恢复。
Objective To study the effect of osimertinib,an epidermal growth factor receptor(EGFR)inhibitor,on the expression of inflammatory factors and tight junction proteins and neurological function recovery after spinal cord injury(SCI)in rats.Methods Totally,60 SD rats were randomly divided into sham group,injury group and osimertinib group.The model of SCI was established in the injury group and osimertinib group.On days 3 and 7 after SCI,the tight junction proteins ZO-1,Occludin and the pro-inflammatory factors IL-1β,TNF-α,COX-2,iNOS,and p-EGFR and EGFR in the spinal cord were detected by Western blotting.Immunofluorescence staining and Western blotting were used to detect the expression of GFAP and CD11 b in spinal cord tissue of rats in each group 7 days after SCI.The demyelination was evaluated by Luxol Fast Blue stain,motor function assessed by the BBB score,and urination function tested by bladder residual urine volume.Results(1)On days 3 and 7 after SCI,the expression of pro-inflammatory factors IL-1β,TNF-α,COX-2 and iNOS in osimertinib group were significantly lower than those in injury group(all P<0.05).(2)On days 3 and 7 after SCI,the expression of tight junction proteins ZO-1 and occludin in osimertinib group were significantly higher than those in injury group(all P<0.05).(3)On days 3 and 7 after SCI,the activation of EGFR in osimertinib group was significantly lower than that in injury group(P<0.05).(4)On day 7 after SCI,the expression of GFAP and CD11 b in the injury group was significantly increased,while the expression of both in the osimertinib group was significantly decreased compared with the injury group(both P<0.05).(5)The area of the demyelination region in spinal cord in the osimertinib group was significantly decreased compared to injury group(P<0.05).The BBB scores were significantly higher in the osimertinib group than in the injury group(P<0.05).The residual urine was significantly less in the osimertinib group than in the injury group(P<0.05).Conclusion Osimertinib,an EGFR inhibitor,c
作者
李在望
曹婷婷
王倩
涂景梅
韩晶
Li Zaiwang;Cao Tingting;Wang Qian(De partment 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,China;Department of Neurology,Yancheng First People's Hos pital,Yancheng 224001,China)
出处
《华中科技大学学报（医学版）》
CAS
CSCD
北大核心
2021年第3期297-302,共6页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基金
国家自然科学基金资助项目(No.81671219,No.82071364)
深圳市自然科学基金资助项目(No.JCYJ20190806145812589)。
关键词
脊髓损伤
奥希替尼
紧密连接蛋白
致炎因子
spinal cord injury
osimertinib
tight junction proteins
pro-inflammatory factors
