阿魏酸钠联合人参皂苷Rg_1镇痛作用及其机制

Analgesic Effects and Mechanisms of Sodium Ferulate and Ginsenoside Rg_1

目的：观察阿魏酸钠（SF）联合人参皂苷Rg1（Rg1）镇痛作用并探讨其作用机制.方法：采用小鼠和大鼠两种动物,将动物分为SF低、中、高剂量组（2.5,5,10 mg·kg^-1）,Rg1低、中、高剂量组（5,10,20 mg·kg^-1）,复方（SF和Rg1联合用药）低、中、高剂量组（2.5＋5,5＋10,10＋ 20） mg·kg^-1并设置对照组,ig给药5d后采用小鼠热板法,小鼠醋酸扭体法,大鼠福尔马林法观察SF和Rg1单用及联合应用的镇痛作用;采用全细胞膜片钳技术观察SF和Rg1单用及联合应用对瞬时感受器电位香草酸亚型1（TRPV1）的影响.结果：55℃热板,0.6％醋酸溶液0.02 mL·g^-1,5％福尔马林溶液0.1mL可致动物出现明显疼痛反应,SF中、高剂量组,Rg1高剂量组,复方低、中、高剂量组对3种疼痛模型均有较好的镇痛作用（P ＜0.05,P＜0.01）,且复方效果明显优于SF或Rg1单用（P＜0.05,P＜0.01）;1μmo1· L^-1辣椒素（CAP）可激活TRPV1产生特异性内向电流,SF,Rg1及复方组对该电流均具有一定的抑制作用,且复方组抑制作用强于SF和Rg1组（P＜0.05,P＜0.01）.SF,Rg1,复方的IC50及95％置信区间分别为32.4（27.5 ～38.7）,82.6（71.0 ～98.4）,30.6（20.2 ～41.0） mg·L^-1,等效应曲线图显示,SF和Rg1对CAP诱导的TRPV1电流的抑制具有协同效应.结论：SF和Rg1合用具有较好的镇痛作用,对TRPV1的协同抑制作用可能是其机制之一.

Objective：The aim of this study was to ascertain the synergistic analgesic interaction and potential mechanism of sodium ferulate （SF） and ginsenoside Rg1 （Rg1）.Method：Mice and rats were divided into SF low,medium and high dose groups,Rg1 low,medium and high dose groups,the combination low,medium and high dose groups and the control groups.After 5 days of intragastric administration,the hot plate test,the acetic acid writhing test and the formalin test were used to observe the analgesic effects of SF,Rg1 and the combination.The whole-cell patch-clamp was used to observe the effects of SF,Rg1 and on transient receptor potential vanilloid 1 （TRPV1）.Result：Hot plate 55 ℃,0.6% acetic acid solution 0.02 mL · g^-1,5% formaldehyde solution 0.1 mL caused obvious pain responses.The medium and high dose groups of SF,the high dose group of Rg1 and the low,medium and high dose groups of the combination showed good analgesic effects on the three models （P 〈 0.05,P 〈 0.01）,and the effects of the combination were better than SF or Rg1 administrated alone （P 〈 0.05,P 〈 0.01）.1 μmol ·L^-1 capsaicin （CAP） activated TRPV1 and induced specific inward current,SF,Rg1 and the combination inhibited the current and the inhibition of the combination was stronger than SF and Rg1 group （P 〈 0.05,P 〈 0.01）.The 50% inhibition concentration （IC50） and 95% confidence interval of SF,Rg1 and the combination were 32.4 （27.5-38.7）,82.6 （71.0-98.4）,71.0 （20.2-41.0） mg ·L^-1respectively.The isobologram showed that the inhibition of SF and Rg1 on TRPV1 had a synergistic effect.Conclusion：The combination of SF and Rg1 had analgesic effect,the synergistic inhibition of may be one of its mechanisms.