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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5 d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0.1 mL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);1μmol·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: To observe the analgesic effect of sodium ferulate (SF) combined with ginsenoside Rg1 (Rg1) and to explore its mechanism. Methods: The animals were divided into SF low, medium and high dose groups (2.5, 5 and 10 mg · kg -1), Rg1 low, medium and high dose groups (5, 10, (2.5 +5, 5 +10, 10 +20) mg · kg-1 in the low, medium and high dose groups (SF and Rg1 combined group) and the control group d after the use of mouse hot plate method, mouse acetic acid writhing method, rat formalin method SF and Rg1 single and combined analgesic effect observed; whole cell patch clamp technique to observe the SF and Rg1 single and Effect of Combination Therapy on Temporal Receptor Potential for Vanilloid Type 1 (TRPV1). Results: In the hot plate of 55 ℃, 0.02 mL · g-1 of 0.6% acetic acid solution and 0.1 mL of formalin solution could induce significant pain reaction in animals. SF, high dose group, high dose Rg1 group, (P <0.05, P <0.01), and the compound effect was significantly better than SF or Rg1 alone (P <0.05, P <0.01); 1μmol L-1 capsaicin (CAP) can activate TRPV1 to produce specific inward current, SF, Rg1 and compound group have certain inhibitory effect on this current, and the inhibitory effect of compound group is stronger than SF and Rg1 group (P <0.05, P <0.01). The IC50 and 95% confidence intervals of SF, Rg1 and compound were 32.4 (27.5-38.7), 82.6 (71.0-98.4) and 30.6 (20.2-41.0) mg · L-1, respectively. The inhibition of CAP-induced TRPV1 current has a synergistic effect. Conclusion: Combination of SF and Rg1 has good analgesic effect and synergistic inhibitory effect on TRPV1 may be one of its mechanisms.