丙戊茶碱对神经病理性疼痛大鼠的镇痛作用及机制

Analgesic Effect of Propentofylline in Rats with Neuropathic Pain and Its Mechanism

目的观察丙戊茶碱对大鼠坐骨神经分支选择性损伤(SNI)致神经病理性疼痛的镇痛作用。方法将96只雄性SD大鼠随机分4组:假手术组(Sh)、模型组(S)、鞘内注射丙戊茶碱组(P1)及腹腔内注射丙戊茶碱组(P2)。其中S组和P1组造模后分别单次鞘内注射盐水20μl和丙戊茶碱20μ(l0.05μg/μl);P2组造模后单次腹腔内注射丙戊茶碱1ml(1mg/kg)。记录全组动物术前1d及术后1,3,7,14,21d的机械缩足反射阈值(MWT)和热缩足反射维持时间(TWD),并在术后各时点随机选6只大鼠,取脊髓腰膨大,用免疫印迹法检测腺苷A1受体(A1-AR)蛋白量的变化,用ELISA法检测TNF-α和IL-1β含量的变化。结果S组术后出现明显的MWT下降和TWD延长,与术前及Sh组术后各时点比较有显著性差异(P<0.05)。与S组比较P1、P2组行为学指标的变化幅度大(P<0.05),且P1组行为学指标的变化幅度大于P2组。S组TNF-α和IL-1β的含量术后均增加,与Sh组比较差异有统计学意义(P<0.01);P1和P2组TNF-α和IL-1β的含量升高的幅度小,与S组比较有统计学差异(P<0.05);P1、P2组腺苷A1受体的表达量升高明显,与S组比较有统计学差异(P<0.05)。结论丙戊茶碱能抑制SNI大鼠炎性介质的释放,且在脊髓水平增强A1-AR的激活,对SNI大鼠神经病理性疼痛的抑制发挥重要的作用。

Objective To investigate the analgesic effect of propentofylline on neuropathic pain in rat model of spared nerve injury（SNI） on the sciatic nerve.Methods Adult male SD rats were randomly divided into 4 groups：group Sh（sham operated group）,group S（SNI model group in which rats received intrathecal injection of 20 μl normal saline）,group P1（in which rats received intrathecal injection of 20 μl propentofylline）,and group P2（in which rats received intraperitoneal injection of 1 ml propentofylline）.Mechanical withdrawal threshold（MWT）and thermal withdrawal duration（TWD）were determined on preoperative day 1 and postoperative days 1,3,7,14,and 21.In each group,6 rats were randomly selected on postoperative days 1,7,14,and 21,and L4-L5 spinal segments were removed.The expression of adenosine A1 receptor（A1-AR）and the levels of TNF-α and IL-1β were determined by Western blot and ELISA,respectively.Results Compared with group Sh,MWT significantly decreased and TWD significantly prolonged at each time point in group S（P〈0.05）.The changes in behavior were greater in groups P1 and P2 than in group S（P〈0.05）,and the behavioral changes in group P1 were greater than those in group P2.There were significant differences in the levels of TNF-α and IL-1β between groups S and Sh,and compared with group S,the increase in the levels of TNF-α and IL-1β in groups P1 and P2 was less than that in group S（P〈0.05）.The expression of adenosine A1 receptor increased more significant in groups P1 and P2 than in group S（P〈0.05）.Conclusion Propentofylline could inhibit the release of inflammatory mediators and promote the activation of A1-AR,and thus it may play important roles in inhibiting neuropathic pain in rat model of SNI.