摘要
目的:观察倍他米松二丙酸酯-聚乙二醇-聚乳酸(B DP-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B DP-PEG-PLA微球,分别以PLA的数均分子量20、30和70 k D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)、20kD组、30kD组和70kD组。观察术前1d,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,B DP组抑制痛觉过敏(MWT下降和TWL缩短)持续至5 d (P<0.05);20 k D组、30 k D组和70 k D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, B DP组、20 k D组、30 k D组和70 k D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 k D组术后10 d较CCI组和B DP组磷酸化ERK表达减少(P<0.05)。结论坐骨神经单次注射B DP-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。
Objective To investigate the effect of betamethasone dipropionate-ploy ethylene glycol-poly lactic acid (B DP-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 B DP-PEG-PLA microparticles were prepared,which were respectively denoted as the PLA number-average molecular weight 20 k D, 30 k Dand 70 k D.Altogether 96 Wistar rats were randomly divided into 6 groups (n=16):sham operation group (S H group),model group (CCI group),betamethasone dipropionate group (B DP group),20 k Dgroup,30 k Dgroup,and 70 k Dgroup.Mechanical withdraw threshold (MWT)and thermal withdrawal latency (TWL)of the rats were meas-ured on preoperative day 1,postoperative day 3,5,7,10,13 and 15.Activation of spinal ERK was assessed on post-operative day 3 and 10 by immunohistochemistry.Results Compared with that of the CCI group,the analgesic effect of B DP group continued over a period of 5 days (P〈 0.05 );the analgesic effects of 20 k Dgroup,30 k Dgroup and 70 k Dgroup lasted for 7,10 and 13 days,respectively (P all 〈0.05).The expression of spinal pERK was suppressed in B DP group,20 k Dgroup,30 k Dgroup and 70 k Dgroup on postoperative day 3 (P〈0.05 );pERK expression in 70 k Dgroup was lower than that in CCI group and B DP group on postoperative day 10 (P〈0.05).Conclusion Sin-gle injection of B DP-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.
出处
《山东大学学报(医学版)》
CAS
北大核心
2014年第10期35-39,44,共6页
Journal of Shandong University:Health Sciences
基金
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)
关键词
倍他米松二丙酸酯
聚乙二醇-聚乳酸
微球
慢性压迫性损伤
细胞外信号调节激酶
Betamethasone dipropionate Poly ethylene glycol-poly lactic acid Microparticle Chronic constriction injury Extracellular signal-regulated kinase