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山东大学学报（医学版） ›› 2014, Vol. 52 ›› Issue (10): 35-39,44.doi: 10.6040/j.issn.1671-7554.0.2014.247

• 基础医学 • 上一篇    下一篇

倍他米松二丙酸酯缓释微球对大鼠神经病理性疼痛的镇痛作用及对脊髓细胞外信号调节激酶的影响

丁超1, 胡启雅1, 黄海真1, 郭亚秋1, 裴淼1, 朱庆增2, 齐峰1   

  1. 1. 山东大学齐鲁医院麻醉科, 山东 济南 250012;
    2. 山东大学化学与化工学院, 山东 济南 250100
  • 收稿日期:2014-04-21 修回日期:2014-09-05 出版日期:2014-10-10 发布日期:2014-10-10
  • 通讯作者: 齐峰。E-mail：qifeng66321@sina.com；朱庆增。E-mail：qzzhu@sdu.edu.cn E-mail:qifeng66321@sina.com；qzzhu@sdu.edu.cn
  • 基金资助:
    国家自然科学基金（81171864）；山东省自然科学基金（ZR2012HM097）；山东大学自主科技创新基金（2012JC017）

Effect of slow-released betamethasone dipropionate microparticles on neuropathic pain in rat spinal cord and expression of extracellular signal-regulated kinase

DING Chao1, HU Qiya1, HUANG Haizhen1, GUO Yaqiu1, PEI Miao1, ZHU Qingzeng2, QI Feng1   

  1. 1. Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
    2. School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, Shandong, China
  • Received:2014-04-21 Revised:2014-09-05 Online:2014-10-10 Published:2014-10-10

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摘要： 目的 观察倍他米松二丙酸酯-聚乙二醇-聚乳酸（BDP-PEG-PLA）微球对大鼠坐骨神经慢性缩窄性损伤（CCI）所致神经病理性疼痛的镇痛作用，及对脊髓细胞外信号调节激酶（ERK）的影响。方法 制备3种BDP-PEG-PLA 微球，分别以PLA的数均分子量20、30和70 kD表示。96只雄性Wistar大鼠随机分6组（n=16）：假手术组（SH组）、模型组（CCI组）、倍他米松二丙酸酯组（BDP组）、20 kD组、30 kD组和70 kD组。观察术前1 d，术后3、5、7、10、13及15 d的机械缩足反射阈值（MWT）、热缩足反射潜伏期（TWL）。免疫组化方法检测术后3 d和10 d脊髓磷酸化ERK表达。结果 与CCI组相比，BDP组抑制痛觉过敏（MWT下降和TWL缩短）持续至5 d（P<0.05）；20 kD组、30 kD组和70 kD组抑制痛觉过敏分别持续至7、10和13 d（P均<0.05）。与CCI组相比，BDP组、20 kD组、30 kD组和70 kD组术后3 d时脊髓Ⅰ~Ⅱ板层磷酸化ERK表达均减少（P均<0.05），70 kD组术后10 d较CCI组和BDP组磷酸化ERK表达减少（P<0.05）。结论 坐骨神经单次注射BDP-PEG-PLA微球能通过抑制大鼠脊髓ERK的活性达到长效镇痛作用，且与微球数均分子量有关。

关键词: 慢性压迫性损伤, 聚乙二醇-聚乳酸, 微球, 细胞外信号调节激酶, 倍他米松二丙酸酯

Abstract: Objective To investigate the effect of betamethasone dipropionate-ploy ethylene glycol-poly lactic acid(BDP-PEG-PLA) microparticles on the neuropathic pain in rat sciatic nerve induced by chronic constriction injury (CCI), and on the expression of extracellular signal-regulated kinase (ERK). Methods A total of 3 BDP-PEG-PLA microparticles were prepared, which were respectively denoted as the PLA number-average molecular weight 20 kD, 30 kD and 70 kD. Altogether 96 Wistar rats were randomly divided into 6 groups (n=16): sham operation group (SH group), model group (CCI group), betamethasone dipropionate group (BDP group), 20 kD group, 30 kD group, and 70 kD group. Mechanical withdraw threshold (MWT) and thermal withdrawal latency (TWL) of the rats were measured on preoperative day 1, postoperative day 3, 5, 7, 10, 13 and 15. Activation of spinal ERK was assessed on postoperative day 3 and 10 by immunohistochemistry. Results Compared with that of the CCI group, the analgesic effectof BDP group continued over a period of 5 days (P<0.05); the analgesic effects of 20 kD group, 30 kD group and 70 kD group lasted for 7, 10 and 13 days, respectively (P all <0.05). The expression of spinal pERK was suppressed in BDP group, 20 kD group, 30 kD group and 70 kD group on postoperative day 3 (P<0.05); pERK expression in 70 kD group was lower than that in CCI group and BDP group on postoperative day 10 (P<0.05). Conclusion Single injection of BDP-PEG-PLA microparticles in sciatic nerves provides long-term analgesic effect by suppressing spinal ERK activation in CCI rats, which is related to the number-average molecular weight of microparticles.

Key words: Betamethasone dipropionate, Microparticle, Chronic constriction injury, Poly ethylene glycol-poly lactic acid, Extracellular signal-regulated kinase

中图分类号: 

  • R614
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