利鲁唑对糖尿病神经病理性疼痛大鼠背根神经节Nav1.7表达的影响

EFFECT OF RILUZOLE ON EXPRESSION OF Nav1.7 IN DORSAL ROOT GANGLION NEURONS IN RATS WITH DIABETIC NEUROPATHIC PAIN

目的:探讨镇痛药利鲁唑(riluzole)对糖尿病神经病理性疼痛大鼠背根神经节(dorsal root ganglion,DRG)Nav1.7表达的影响。方法:雄性SD大鼠108只,采用随机数字表法,将其分为4组(n=27):对照组(C组)、模型组(DNP组)、10%溶剂DMSO组(DNP+DMSO组)和利鲁唑组(DNP+riluzole组)。观察STZ注射前1 d及注射后3、7、10、14、21、28 d测定缩足反射机械刺激阈值(paw withdrawal mechanical threshold,PWMT)和缩足反射热辐射潜伏期(paw withdrawal thermal latency,PWTL)。10%DMSO组和利鲁唑组于STZ注射15 d起分别腹腔注射10%DMSO或利鲁唑4 mg/kg,1次/日,连续7 d,于21、28 d测定PWMT和PWTL。行为学测试完成后选择21 d大鼠用免疫荧光和Western blot方法检测大鼠DRG中Nav1.7的表达。结果:与C组比较,DNP组大鼠PWMT降低,PWTL缩短,DRG中Nav1.7的表达上调,差异有统计学意义(P<0.05);与DNP组比较,DNP+DMSO组大鼠在腹腔注射10%DMSO后,PWMT、PWTL和Nav 1.7的表达无明显改变,与DNP+DMSO组和DNP组比较,DNP+riluzole组大鼠在腹腔注射利鲁唑后,PWMT明显升高,PWTL明显延长,DRG中Nav 1.7的表达下调,差异有统计学意义(P<0.05)。结论:利鲁唑可通过抑制DNP大鼠DRG中Nav 1.7表达,从而减轻大鼠DNP。

Objective：To investigate the effect of riluzole,an analgesic on the expression of Nav1.7 in dorsal root ganglion （DRG） neurons in a rat model of diabetic neuropathic pain （DNP）.Methods：108 male SD rats weighing 200～220 g were randomly divided into 4 groups （n =27 each）：control group （group C）,DNP group,DNP＋DMSO group and DNP＋riluzole group.Diabetes were induced with streptozocin （70 mg/kg） injected subcutaneously.Paw withdrawal mechanical threshold （PWMT） and paw withdrawal thermal latency （PWTL） were measured 1 day before and 3,7,10,14,21,28 days after streptozocin injection.10％ DMSO and riluzole （4 mg/kg） were given intraperitoneally once a day for 7 consecutive days starting at day 15 after streptozocin injection in DNP＋DMSO and DNP＋riluzole groups respectively,and PWMT and PWTL were measured at day 21,28 for the two groups.The expression of Navl.7 in DRG neurons was determined at day 21 after streptozocin injection by immunofluorescent staining and Western blot after the ethology test was completed.Results：Compared with group C,PWMT and PWTL were significantly decreased,and Nav1.7 expression was significantly increased in DNP,DNP＋DMSO and DNP＋riluzole groups （P ＜ 0.05）.Compared with DNP＋DMSO and DNP groups,PWMT and PWTL were significantly increased,and Nav1.7 expression was significantly decreased in DNP＋riluzole group after intraperitoneal injection of riluzole （P ＜ 0.05）.There was no significant difference in the parameters mentioned above between DNP and DNP＋DMSO groups.Conclusion：Riluzole can attenuate DNP by inhibiting the expression of Nav1.7 in DRG neurons.