奥希替尼对大鼠脊髓损伤后血脊髓屏障通透性的影响

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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（SCI）后血脊髓屏障通透性的影响。方法 60只8周龄雌性SD大鼠（200～250 g）按照随机数字表法分为假手术组（n = 20)和SCI模型组（n = 40），采用随机数字表法将40只SCI模型大鼠分为损伤组和奥希替尼组，每组20只。奥希替尼组给予浓度为0.4 mg/mL奥希替尼溶液灌胃（2 mL/d），假手术组和损伤组给予生理盐水灌胃（2 mL/d），三组均干预3 d。SCI后3 d测定脊髓组织含水量，Western blot技术检测水通道蛋白-4（AQP-4）表达量，采用伊文思蓝（EB）染料渗漏实验及免疫荧光技术测定脊髓白蛋白含量评估血脊髓屏障通透性变化。采用Basso-Beattie-Bresnahan（BBB）评分评估大鼠运动功能。结果 SCI后3 d 奥希替尼组脊髓含水量明显低于损伤组（P ＜ 0.05）；奥希替尼组AQP-4蛋白表达量明显低于损伤组（P ＜ 0.01）；奥希替尼组脊髓组织EB染料聚集较损伤组少，EB荧光强度较损伤组弱（P ＜ 0.05）；奥希替尼组白蛋白免疫荧光强度较损伤组弱。奥希替尼组总体BBB评分高于损伤组（P ＜ 0.05）。结论 EGFR抑制剂奥希替尼可改善SCI后血脊髓屏障的破坏并减轻脊髓继发性损伤，促进神经功能恢复。

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	李在望1 曹婷婷2 王倩1 涂景梅1 韩晶1

关键词 ：奥希替尼, 脊髓损伤, 血脊髓屏障, 神经功能

Abstract：Objective To investigate the effects of epidermal growth factor receptor (EGFR) inhibitor Osimertinib on blood-cord barrier permeability after spinal cord injury (SCI) in rats. Methods A total of sixty eight week-old female SD rats (200 to 250 g) were divided into sham operation group (n = 20) and SCI model group (n = 40) according to random number table method. The 40 SCI model rats were divided into injury group and Osimertinib group by random number table method, with 20 rats in each group. The Osimertinib group was gavaged with 0.4 mg/mL Osimertinib solution (2 mL/d), and the sham operation group and the injury group were gavaged with normal saline (2 mL/d). All the three groups were treated for 3 days. The water content of spinal cord tissue was determined 3 days after SCI, the expression of aquaporin-4 (AQP-4) protein was detected by Western blot, the evans blue (EB) dye leakage test and the albumin content of spinal cord were determined by immunofluorescence technique to evaluate the changes of blood and spinal cord barrier permeability. Basso-Beattie-Bresnahan (BBB) score was used to evaluate the motor function of rats. Results The water content of spinal cord in Osimertinib group at 3 days after SCI was significantly lower than that in injury group (P ＜ 0.05). The expression of AQP-4 protein in Osimertinib group was significantly lower than that in injury group (P ＜ 0.01). The concentration of EB dye in spinal cord tissue in Osimertinib group was less than that in injury group, and the fluorescence intensity of EB was weaker than that in injury group (P ＜ 0.05). The immunofluorescence intensity of albumin in Osimertinib group was weaker than that in injury group. The overall BBB score of Osimertinib group was significantly higher than that of injury group (P ＜ 0.05). Conclusion The EGFR inhibitor Osimertinib can improve the damage of the blood-cord barrier after SCI and alleviate the secondary injury of the spinal cord, and promote the recovery of neurological function.

Key words： Osimertinib Spinal cord injury Blood spinal cord barrier Neurologic function

基金资助:国家自然科学基金资助项目（81671219、820713 64）；
广东省深圳市科技计划项目（JCYJ20190806145812589）。

作者简介: 李在望（1977.6-），男，医学博士，副主任医师；研究方向：中枢神经损伤。

引用本文:

李在望1 曹婷婷2 王倩1 涂景梅1 韩晶1. 奥希替尼对大鼠脊髓损伤后血脊髓屏障通透性的影响[J]. 中国医药导报, 2021, 18(14): 9-12,26.
LI Zaiwang1 CAO Tingting2 WANG Qian1 TU Jingmei1 HAN Jing1. Effect of Osimertinib on blood-cord barrier permeability after spinal cord injury in rats. 中国医药导报, 2021, 18(14): 9-12,26.

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