正天丸的镇痛作用及机制研究

摘要

Objective:To investigate the analgesic effect and molecular mechanisms of Zhengtian Pill (ZTP) to provide the pharmacological evidence of migraine therapy.Methods:The hot plate test,acetic acid-induced writhing test and formalin test were used to assess the analgesic effect of ZTP after administration for 5 days.After the formalin test,Prostaglandin E2(PGE2) and nitric oxide (NO) in mice serum,glutamate (Glu) and calcitonin gene related peptide (CGRP) in mice brain were measured by Ultraviolet spectrophotometry,Nitrate reductase approach and ELISA kits,respectively,to analyze their changes in content via the intervention of ZTP.Results:ZTP elevated pain threshold to thermal stimuli,also prolonged latency time to writhing reaction and decreased number of writhing in acetic acid test in mice.Furthermore,ZTP significantly reduced total time of licking,biting the injected paw in the biphasic responses induced by formalin in mice.Meanwhile,ZTP markedly reduced content of PGE2 in mice serum,Glu and CGRP in mice brain,whereas ZTP increased NO level in peripheral mice serum.Conclusions:ZTP can exert analgesic effect on nociception induced by thermal,acetic acid and formalin stimuli.These molecular mechanisms involve not only in inhibition of release of central Glu,CGRP and peripheral PGE2,but also in promotion of synthesis of peripheral NO.%目的:考察正天丸镇痛作用以及镇痛机制,为其治疗偏头痛提供药理学依据.方法:小鼠连续预给药5d,采用热板、冰乙酸、甲醛3个经典疼痛动物模型观察正天丸对疼痛小鼠的镇痛作用;采用紫外分光光度法测定甲醛疼痛模型各组小鼠血清中前列腺素E2(PGE2)和脑组织中谷氨酸(Glu)含量,硝酸还原酶法测定血清中一氧化氮(NO)含量以及ELISA法检测脑中降钙素基因相关肽(CGRP)含量,探讨其镇痛的作用机制.结果:正天丸能提高热刺激小鼠的痛阈值,延长冰乙酸所致的小鼠扭体反应潜伏期,减少扭体次数,并能显著缩短甲醛致病小鼠的Ⅰ相和Ⅱ相舔、咬足时间;明显降低甲醛致疼痛模型小鼠血清PGE2、脑组织Glu和CGRP含量,显著提高外周血清NO含量.结论:正天丸具有明显的镇痛作用,其镇痛机制与抑制中枢Glu、CGRP释放、降低外周疼痛介质PGE2含量、促进外周NO合成有关.