三种不同大鼠蛛网膜下腔给药方式的比较

Comparison of different methods for drug delivery via the lumbar spinal subarachnoid space in rats

目的比较三种大鼠蛛网膜下腔给药途径的优缺点。方法将成年雄性SD大鼠分为3组,分别作如下处理:重复穿刺(1次/d),椎板切除置管以及经皮置管。设空白对照组。记录操作前后大鼠体质量变化;评估其一般行为及神经生物学行为;Rota-Rod跑步行为学测试,检查运动平衡与协调功能变化;痛敏刺激测试其对伤害的感受性反应。HE染色评价局部炎症反应,并行甲苯胺蓝染色试验评价不同方法的给药精度。结果重复穿刺组成功率较低,并且引起较多并发症:包括异常的神经行为学表现以及严重的运动功能障碍、痛觉过敏、脊髓背侧严重的局部炎症反应。留置导管可以方便进行后续给药,适合长期的药理学及行为学研究。经椎板切除置管创伤大,严重影响动物的生理功能,并且容易引起脊髓额外损伤(P=0.03)。经皮置管具有最高的手术成功率,且创伤小,仅引起轻度的脑脊液漏、微弱的感觉运动障碍以及脊髓背侧极轻微的组织病理学改变,给药精度高(P=0.002)。结论3种方法相比,经皮置管是一种安全、有效、精确的重复给药途径。

Objective To compare 3 commonly used methods for drug delivery via the lumbar spinal subarachnoid space in rats.Methods We compared the effects of 3 methods for drug delivery via the lumbar spinal subarachnoid space in Sprague Dawley rats,namely acute needle puncture,chronic catheterization via laminectomy,and non-laminectomized catheterization.Body weight changes of the rats were measured,and their general and neurological conditions were assessed after the surgeries.The motor function of the rats was examined using rota rod test both before and after the surgeries.Nociceptive tests were performed to assess nociception of the rats.HE staining was used to examine local inflammation caused by the surgeries in the lumbar spinal cord tissue,and lidocaine paralysis detection and toluidine blue dye assay were used to confirm the precision of drug delivery using the 3 methods.Results Both needle puncture and catheterization via laminectomy resulted in a relatively low success rate of surgery and caused neurological abnormalities,severe motor dysfunction,hyperalgesia,allodynia and local inflammation.Catheterization without laminectomy had the highest success rate of surgery,and induced only mild agitation,slight cerebral spinal fluid leakage,mild sensory and motor abnormalities,and minimum pathology in the lumbar spinal cord.Catheterization without laminectomy produced less detectable effects on the behaviors in the rats and was well tolerated compared to the other two methods with also higher precision of drug delivery.Conclusion Catheterization without laminectomy is a safe,accurate and effective approach to lumbar drug delivery in rats.