白藜芦醇通过调节Ca^(2+)浓度对小鼠外周疼痛的影响及作用机制

Analgesic effect of resveratrol on peripheral pain in mice via regulating the concentration of Ca^(2+) and its mechanism

目的:探讨Ca^(2+)通道,特别是L型钙通道和钙/咖啡因敏感池,是否参与白藜芦醇的镇痛作用。方法:小鼠单独使用反式白藜芦醇(10、20、40 mg/kg,p.o.)30 min后,进行甩尾实验,记录痛阈值,评价对痛觉的反应;白藜芦醇(10、20 mg/kg,p.o.)联合使用MK801(0.5 mg/kg,i.p.)或尼莫地平(2.5、5、10 mg/kg,i.p.)或Ca Cl2(25、50、100、200 nmol/只,i.c.v.)或兰尼定(0.25、0.5、1、2 nmol/只,i.c.v.)或EGTA(5、15、30 nmol/只,i.c.v.)30 min后,同样进行甩尾实验,记录痛阈值,评价对痛觉的反应。结果:甩尾实验中,白藜芦醇增加小鼠的甩尾潜伏期(P<0.01)。联合应用MK801或尼莫地平增强了白藜芦醇的镇痛作用(P<0.05),中枢给予Ca^(2+)后,降低了白藜芦醇的镇痛作用(P<0.05);而联合使用EGTA或兰尼定增强了白藜芦醇的镇痛作用(P<0.05)。结论:当白藜芦醇联合使用MK801或尼莫地平或EGTA或兰尼定时,白藜芦醇产生的镇痛作用明显增强;而白藜芦醇联合使用Ca^(2+)后,白藜芦醇产生的镇痛作用明显降低。白藜芦醇可能是通过Ca^(2+)通道和钙库/咖啡因敏感池发挥镇痛作用。

Objective： To explore whether Ca2＋, especially L-voltage-gated Ca2＋ channels and Ca2＋/caffeine-sensitive pools are involved in a algesic, effects and mechanisms in resveratrol-induced antinociception. Methods： Tail flick test was used to assess allodynia in mice treated with resveratrol （10, 20, 40 mg/kg, p.o.） alone or the combination of resveratrol or MK801 （0.5 mg/kg, i.p.） or nimodipine （2.5, 5, 10 mg/kg, i.p.） or CaCl2 （25, 50, 100, 200 nmol per mouse, i.c.v.） or ryanodine （0.25, 0.5, 1, 2 nmol per mouse, i.c.v.） or EGTA （5, 15, 30 nmol per mouse, i.c.v.）. Results： The results showed that resveratrol increased the tail flick latency in the tail flick test （P〈0.01）. The effect of resveratrol was strengthened by MK801 or nimodipine （P〈0.05）. Central administration of Ca2＋, however, diminished the antinociceptive effect of resveratrol （P〈0.05）. In contrast EGTA or ryanodine administered centrally improved the antinociceptve effect （P〈0.05）. Conclusion： The effect of resveratrol was enhanced by MK801, nimodipine, EGTA and ryanodine, while central administration of Ca2＋, reduced the antinociceptive effects of resveratrol. The findings suggest that resveratrol produces effects on antinociception through regulation of calcium channels and calcium/caffeine-sensitive pools.