CAJ | 학술논문

目的评价加巴喷丁对奥沙利铂诱发神经病理性痛小鼠背根神经节(DRG)神经元高电压激活钙通道的影响.方法清洁级雄性昆明小鼠,体重20～25 g,6周龄.采用腹腔注射奥沙利铂3mg/kg的方法制备神经病理性痛模型.取模型制备成功的小鼠41只,采用随机数字表法,将小鼠随机分为神经病理性痛组(NP组,n=20)和加巴喷丁组(G组,n=21),另取10只正常小鼠为正常对照组(C组).G组于奥沙利铂给药后第3天腹腔注射加巴喷丁100mg/kg,NP组及C组给予等容量的生理盐水,每天1次,连续3 d.于加巴喷丁给药前即刻、给药后1～3 d(T1-4)时测定小鼠双后肢机械缩足阈值(MWT).于最后一次MWT测定后,取两侧L4,5节段DRG,分离DRG神经元,采用全细胞膜片钳记录峰电流密度,拟合DRG神经元高电压激活钙通道激活曲线和稳态失活曲线,计算半数激活电位(Va1/2)和半数失活电位(Vi1/2).结果与C组比较,NP组T1～4时、G组T1时MWT降低,NP组峰电流密度和Vi1/2升高(P＜0.05),Va1/2差异无统计学意义,G组峰电流密度、Vi1/2和Va1/2差异无统计学意义(P＞0.05);与NP组比较,G组T2-4时MWT升高,峰电流密度和Vi1/2降低(P＜0.05).结论加巴喷丁减轻小鼠奥沙利铂诱发神经病理性痛的机制可能与抑制DRG神经元高电压激活钙通道电流,促进通道失活有关.
목적 평개가파분정대오사리박유발신경병이성통소서배근신경절(DRG)신경원고전압격활개통도적영향.방법 청길급웅성곤명소서,체중20～25 g,6주령.채용복강주사오사리박3mg/kg적방법제비신경병이성통모형.취모형제비성공적소서41지,채용수궤수자표법,장소서수궤분위신경병이성통조(NP조,n=20)화가파분정조(G조,n=21),령취10지정상소서위정상대조조(C조).G조우오사리박급약후제3천복강주사가파분정100mg/kg,NP조급C조급여등용량적생리염수,매천1차,련속3 d.우가파분정급약전즉각、급약후1～3 d(T1-4)시측정소서쌍후지궤계축족역치(MWT).우최후일차MWT측정후,취량측L4,5절단DRG,분리DRG신경원,채용전세포막편겸기록봉전류밀도,의합DRG신경원고전압격활개통도격활곡선화은태실활곡선,계산반수격활전위(Va1/2)화반수실활전위(Vi1/2).결과 여C조비교,NP조T1～4시、G조T1시MWT강저,NP조봉전류밀도화Vi1/2승고(P＜0.05),Va1/2차이무통계학의의,G조봉전류밀도、Vi1/2화Va1/2차이무통계학의의(P＞0.05);여NP조비교,G조T2-4시MWT승고,봉전류밀도화Vi1/2강저(P＜0.05).결론 가파분정감경소서오사리박유발신경병이성통적궤제가능여억제DRG신경원고전압격활개통도전류,촉진통도실활유관.
Objective To investigate the effects of gabapentin on high-voltage-activated calcium currents in dorsal root ganglion (DRG) neurons in mice with oxaliplatin-induced neuropathic pain (NP). Methods Pathogen-free male Kunming mice aged 6 weeks weighing 20-25 g were used in this study. NP was induced by injection of intraperitoneal oxaliplatin 3 mg/kg. Successful induction of NP was defined as the mechanical paw withdrawal threshold (MWT) measured at 3 d after oxaliplatin administration decreased to 40% of the baseline ( before administration of oxaliplatin). Forty-one mice in which NP was successfully induced were randomly divided into 2 groups: NP group ( n = 20) and gabapentin group (group G, n = 21 ). Another 10 normal mice served as control group (group C). At 3 days after oxaliplatin administration, gabapentin 100 mg/kg was injected intraperitoneally once a day for 3 consecutive days in group G, while C and NP groups received the equal volume of normal saline.MWT to von Fray filament stimulation was measured immediately before and 1-3 days after gabapentin administration (T1-4). After the last measurement of MWT, bilateral L4.5 DRG was collected and neurons were isolated. The high-voltage-activated calcium currents were recorded using whole-cell patch-clamp technique. The peak current density and the voltage where half of the current was activated ( Va1/2 ) or inactivated ( Vi 1/2 ) were calculated. Results Compared with group C, MWT at T1-4 was decreased, the peak current density and Vi1/2 were significantly increased in group NP, and MWT at T1 was decreased in group G ( P ＜ 0.05). There was no significant difference in the peak current density, Vi1/2 and Va1/2 between C and G groups ( P ＞ 0.05). MWT at T2-4 was significantly increased, while the peak current density and Vi1/2 were significantly decreased in group G compared with group NP (P ＜ 0.05). Conclusion Gabapentin can reduce oxaliplatin-induced NP in mice through inhibiting high-voltage-activated calcium currents and promoting the inactivation of the channels in DRG neurons.