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

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

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.