课题背景：人们发现将化疗药物和磁性材料一起包封于载体材料中，进入体内后在外磁场作用下使微球聚集于病变部位，可提高靶区内的药物浓度，从而提高疗效，减少用药剂量，降低全身毒副作用。本文观察在外磁场作用下蛛网膜下腔注射自制的亚甲蓝磁性明胶微球对家兔痛阈及体感诱发电位的影响。

临床应用性：实验表明亚甲蓝磁性明胶微球在外磁场作用下可靶向阻滞脊髓背根神经节，提高家兔的痛阈并延长体感诱发电位，具有“感觉-运动”分离阻滞作用，是一种有效的长效靶向神经阻滞剂。

偏倚或不足：实验微球制剂系根据文献及药典自行制备，非行业标准品，属于探索性实验。

摘要

背景：靶向给药系统是一种安全高效的药物传递途径和技术，是一种新的制剂技术和工艺，这种制剂能将药品运送到靶器官或靶细胞，而正常部位几乎不受药物的影响。
目的：实验拟观察亚甲蓝磁性明胶微球在外磁场作用下对家兔痛阈及体感诱发电位的影响，探讨其对脊髓背根神经结靶向神经阻滞的可行性。
设计、时间及地点：随机对照动物实验，于2004-03/2005-04在解放军总医院实验动物中心完成。
材料：雄性新西兰兔24只，体质量2.3~2.8 kg；空白明胶微球（自制）；亚甲蓝磁性明胶微球（自制，载药量为9.8%）。微球系院内药理学实验室高级技师协助制备。
干预：24只家兔随机数字表法分为亚甲蓝磁性微球15 mg 组：在外磁场作用下家兔蛛网膜下腔注射亚甲蓝磁性明胶微球15 mg；空白磁性微球15 mg 组注射单纯磁性微球15 mg；假手术对照组：麻醉和手术步骤同其他组，每组8只。
主要观察指标：连续观察注射药物后家兔下肢的电痛阈、运动功能及脊髓体感诱发电位的变化，最后取脊髓腰骶端作病理切片观察。
结果：24只新西兰兔均进入结果分析。①亚甲蓝磁性微球15 mg 组家兔后肢电痛阈值在给药后第1~6天明显升高，与自身给药前及其他组相比，差异显著（P < 0.05）。②亚甲蓝磁性微球15 mg 组家兔体感诱发电位N1波潜伏期第1~11天明显延长，与自身给药前及其他组相比，差异显著（P < 0.05）；术后13 d 恢复正常。③病理观察显示各组脊髓背角结构、形态正常，神经轴索排列正常，灰白质界限清楚，除假手术对照组外其他组背角均有少数未完全降解的微球，各组的脊髓前角可观察到形态正常的前角运动神经细胞及神经轴索，结构完整。
结论：亚甲蓝磁性明胶微球在外磁场作用下可靶向阻滞脊髓背根神经结，提高家兔的痛阈并延长体感诱发电位，具有“感觉-运动”分离阻滞作用，是一种有效的长效靶向神经阻滞剂。
关键词：亚甲蓝；磁性微球；疼痛；诱发电位

陶利军，孙永海，张宏.亚甲蓝磁性明胶微球在外磁场作用下对家兔痛阈及体感诱发电位的影响[J].中国组织工程研究与临床康复，2008，12(14):2631-2634 [www.zglckf.com/zglckf/ejournal/upfiles/08-14/14k-2631(ps).pdf]

Influence of methylene blue magnetic gelatin microspheres under magnetic field on pain threshold and somatosensory evoked potential in rabbits

Abstract

BACKGROUND: Targeting drug-delivery system is a safe and effective technique to transfer drug and it is a novel drug preparation technique. By this method, the drug can be delivered to targeted organs or cells but not affect normal sites.
OBJECTIVE: To observe the effect of methylene blue magnetic gelatin microspheres (MMGMs) on pain threshold and somatosensory evoked potential in rabbits, and to explore the feasibility of nerve blocking of dorsal root ganglia.
DESIGN, TIME AND SETTING: The randomized controlled animal trial was performed at the Experimental Animal Center of General Hospital of Chinese PLA between March 2004 to April 2005.
MATERIALS: Twenty-four male New Zealand rabbits weighing 2.3-2.8 kg were selected. Empty gelatin microspheres and MMGMs (9.8% of drug-delivery) were self-made assisted by the advanced technicians of Pharmacology Laboratory.
INTERVENTIONS: Twenty-four rabbits were randomly divided into 3 groups (n=8): MMGM group, which was injected with MMGMs (15 mg) in subarachnoid space under the effect of magnetic field; magnetic gelatin microspheres group, which was injected with gelatin microspheres (15 mg) in subarachnoid space; sham operation group (control group), which underwent the same anesthesia and surgery procedure.
MAIN OUTCOME MEASURES: The pain threshold of electronic stimulation, motor function of hind limbs and spinal cord evoked potentials were observed continuously after injection. The pathological section of dorsal root ganglia and Cornu anterius medullae spinalis were made and oberved.
RESULTS: Twenty-four rabbits were included in final analysis. ①The pain threshold of electronic stimulation of hind limbs of MMGMs group significantly increased from the first to sixth days after injection than other groups and before injection (P < 0.05). ②The latency period of N1 wave in spinal cord evoked potentials was significantly extended in MMGMs group compared with other groups and before injection (P < 0.05). The latency period restored to normal condition on postoperative day 13. ③The pathematology of dorsal root ganglia and Cornu anterius medullae spinalis in each group was morphological normal with normal arrangement of neuraxis and clear boundary between gray and white matters. Except for the sham operation group, there were few incompletely degraded microspheres in the dorsal root ganglia.
CONCLUSION: MMGMs play a role of "target nerve block" under the effect of magnetic field and can cause the prolongation of somatosensory evoked potential and dissociation of kineto-sensory function with obvious analgesic effect. So it can serve as a long lasting nerve-blocking drug for the relief of intractable pain.

Tao LJ, Sun YH, Zhang H.Influence of methylene blue magnetic gelatin microspheres under magnetic field on pain threshold and somatosensory evoked potential in rabbits.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(14):2631-2634
[www.zglckf.com/zglckf/ejournal/upfiles/08-14/14k-2631(ps).pdf]