论文部分内容阅读
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.