经寰枕后间隙蛛网膜下腔注射是脊髓损伤模型大鼠可供选择的给药方式  

Subarachnoid injection via the posterior atlanto-occipital interspace is an alternative way of administration in a rat model of spinal cord injury

作　　者：李传鸿 俞兴[1] 杨永栋[1] 杨凯坦 赵赫[1] Li Chuanhong;Yu Xing;Yang Yongdong;Yang Kaitan;Zhao He(Department of Orthopedics,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院骨科,北京市100700

出　　处：《中国组织工程研究》2022年第33期5376-5383,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金面上项目(81973882),项目负责人:俞兴;国家自然科学基金青年科学基金项目(81804119),项目负责人:杨永栋;北京中医药大学东直门医院2020科技创新专项(DZMKJCX-2020-049),项目负责人:俞兴。

摘　　要：背景:蛛网膜下腔给药是脊髓损伤动物实验中常用的干预方式,但目前缺乏可与缓释/控释剂型配合从而减少给药次数、避免蛛网膜下腔内置管的一次性较大剂量蛛网膜下腔内给药的方法。目的:探索一种对于大鼠脊髓损伤模型可以一次性较大剂量给药的蛛网膜下腔注射方法。方法:将SD大鼠随机分为6组:脊髓损伤组采用NYU(New York University)脊髓打击器构建大鼠脊髓损伤模型,蛛网膜下腔注射组经寰枕后间隙将200μL模拟药液(生理盐水)注入蛛网膜下腔,脊髓损伤+蛛网膜下腔注射组在脊髓损伤造模后进行蛛网膜下腔注射,正常对照组无处理,蛛网膜下腔注射假手术组暴露寰枕后膜后关闭切口,脊髓损伤+蛛网膜下腔注射假手术组在脊髓损伤造模后重复蛛网膜下腔注射假手术组的操作。借助甲苯胺蓝染色探索药物注射1.5 h后在蛛网膜下腔内的弥散与分布情况,通过旷场试验、斜板试验、热板试验、体质量测量等验证是否发生蛛网膜下腔注射相关并发症。结果与结论:①各组经寰枕后间隙蛛网膜下腔注射未造成大鼠BBB评分、热板试验与斜板试验结果的异常。②蛛网膜下腔注射假手术组、蛛网膜下腔注射组大鼠术后1周时可恢复术前体质量(P>0.05),脊髓损伤组、脊髓损伤+蛛网膜下腔注射假手术组、脊髓损伤+蛛网膜下腔注射组术后2周时体质量可恢复到术前水平(P>0.05)。③术中及术后未观察到蛛网膜下腔注射引起大鼠中枢神经系统损伤的特殊征象,未见脑脊液/模拟药液外漏,术后大鼠可正常抬头,未出现精神萎靡和自残行为,蛛网膜下腔注射假手术组、蛛网膜下腔注射组未发生排尿排便障碍。④蛛网膜下腔注射后1.5 h,甲苯胺蓝溶液在大鼠蛛网膜下腔内广泛弥散,全段脊髓均有分布。⑤上述数据表明,经寰枕后间隙蛛网膜下腔注射的方法安全可靠,对脊髓损伤大鼠单次给药�BACKGROUND:Subarachnoid injection is a commonly used intervention method in animal experiments of spinal co rd injury.However,at present,there is a lack of methods for one-time large dose of subarachnoid injection that can coope rate with sustained-release/controlled-release dosage forms to reduce the frequency of administration and avoid subarachnoid catheterization.OBJECTIVE:To investigate a method of subarachnoid injection for one-time large dose administration in a rat spinal cord injury model.METHODS:Sprague-Dawley rats were randomly divided into six groups:a spinal cord injury gro u p,a subarachnoid injection group,a spinal co rd injury+s ubarachnoid injection grou p,a subarachnoid injection sham ope ration group,a spinal cord injury+s ubarachnoid injection sham operation group.and a control group.In the spinal cord injury group,New York University spinal cord impactor was used to establish the rat spinal cord injury model.In the subarachnoid injection group,200μL of simulated liquid(stroke-physiological saline solution)was injected into the subarachnoid space of rats via the posterior atlanto-occipital interspace.Rats in the spinal cord injury+subarachnoid injection group received subarachnoid injection after modeling.Rats in the control group were given no treatment.In the subarachnoid injection sham operation group,the posterior atlanto-occipital membrane was exposed and the incision was then sutured.In the spinal cord injury+subarachnoid injection sham operation group,the posterior atlanto-occipital membrane was exposed and the incision was then sutured after modeling.Toluidine blue staining was used to detect drug diffusion and distribution in the subarachnoid space at 1.5 hou rs after injection.Open field test,inclined plane test,hot-plate test,and body mass measurement were used to ve rify the occurrence of subarachnoid injection-related complications.RESULTS AND CONCLUSION:(1)Subarachnoid injection via the posterior atlanto-occipital interspace did not cause abnormal results of Basso-BeattieBresnah

关 键 词：蛛网膜下腔注射 寰枕后间隙 寰枕后膜 脊髓损伤 血脊髓屏障 动物实验 安全性 可靠性 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学]