加巴喷丁对糖尿病神经病理痛大鼠背根神经节Nrf2表达的影响

Effect of gbpapentin on the expression of Nrf2 in dorsal root ganglion neurons of diabetic neuropathic pain rats

目的研究糖尿病神经病理痛大鼠背根神经节(DRG)Nrf2表达的变化,探讨加巴喷丁(gabapentin,GBP)减轻大鼠糖尿病神经病理痛的机制。方法雄性SD大鼠60只,随机分为4组:对照组(C组)、模型组(DNP组)、生理盐水+DNP组(SC+DNP组)和加巴喷丁+DNP组(GBP+DNP组,n=15)。观察STZ注射前1d及注射后3、7、10、14、21、28d测定缩足反射机械刺激阈值(PWMT)和缩足反射热辐射潜伏期(PWTL),SC+DNP组和GBP+DNP组于STZ注射15d起分别腹腔注射生理盐水或加巴喷丁50mg/kg,1次/d,连续7d,并于21、28d测定缩足反射机械刺激阈值和缩足反射热辐射潜伏期。行为学测试完成后选择21d大鼠用免疫荧光和Western印迹方法检测大鼠DRG中Nrf2的表达。结果与C组比较,DNP组和SC+DNP组出现PWMT降低,PWTL缩短,DRG中Nrf2的表达减少(P<0.05);与DNP组比较,GBP+DNP组PWMT升高,PWTL延长,DRG中Nrf2的表达明显增加(P<0.05),SC+DNP组差异无统计学意义(P>0.05)。结论加巴喷丁可能通过上调DNP大鼠DRG中Nrf2表达,从而减轻大鼠DNP。

Objective To investigate the effect of systemic administration of gabapentin on the expression of Nrf2 in dorsal root ganglion neurons in a rat model of diabetic neuropathic pain (DNP). Methods 60 male SD rats weighing 200-220 g were randomly divided into 4 groups (n= 15 each): control group (group C), DNP group, saline group (SC + DNP group) and gabapentin group ( GBP + DNP group). Diabetes was induced with streptozocin (70 mg/ kg) subcutaneously. Paw withdrawal mechanical threshold ( PWMT) and paw withdrawal thermal latency (PWTL) were measured at 1d before and 3,7,10,14,21, and 28 d after streptozocin injection, and 21 and 28 d after administration of gabapentin (50 mg·kg-1 ·d-1 ,once) intraperitoneally. Saline and gabapentin (50 mg·kg-1 · d-1 ) were given intraperitoneally once a day for 7 d starting from 15 d after streptozocin injection in saline and gabapentin groups respectively. The expression of Nrf2 was determined at 21 d after streptozocin injection by immune-histochemistry and Western blot. Results Compared with group C, PWMT ( 3. 95 ± 0. 57) was significantly decreased, PWTL(6.3 ± 0.81) was significantly shorten, Nrf2 in expression was significantly decreased in DNP, SC+DNP and group (P<0.05). Compared with SC+DNP group, PWMT(8.2 ± 0.79) was significantly increased, PWTL(9.7 ± 1.13) was significantly prolonged, Nrf2 expression was significantly increased in GBP+DNP group (P<0.05). There was no significant difference in the parameters mentioned above between DNP and SC+DNP group (P>0.05). Conclusion Systemic administration of gabapentin attenuates diabetic neuropathic pain by enhancing the expression of Nrf2 in DRG neurons.