钙剂对间斑寇蛛毒致痛大鼠行为学及致痛因子表达的影响

THE EFFECT OF CALCIUM GLUCONATE ON THE BEHAVIORS AND EXPRESSION OF PRONOCICEPTIVE MEDIATORS OF RATS AFTER INJECTION OF LATRODECTUS TREDECIMGUTTATUS SPIDERS' TOXIN

目的:观察预先注射葡萄糖酸钙、吗啡、安痛定对间斑寇蛛毒致痛大鼠行为学及致痛因子表达的影响,评估葡萄糖酸钙对抑制间斑寇蛛毒致痛作用的疗效。方法:将雄性SD大鼠120只随机分为钙剂实验组、吗啡对照组和安痛定对照组,实验组大鼠预先尾静脉注射葡萄糖酸钙溶液,吗啡和安痛定对照组大鼠分别预先皮下注射吗啡和安痛定溶液,随后三组大鼠分别足底注射4种浓度的间斑寇蛛毒素,记录三组大鼠不同时间缩足次数,并应用免疫组织化学分析大鼠脊髓致痛因子P2X3受体、P物质、CGRP的表达水平。结果:(1)当毒素浓度为10μl/kg,15 min时,吗啡的镇痛作用优于安痛定,而钙剂镇痛效果最差;1 h时,吗啡及安痛定的镇痛效果较15 min时明显,钙剂的作用更优于吗啡及安痛定(P<0.05)。毒素浓度为300μl/kg,15 min、30 min时钙剂的镇痛作用优于吗啡和安痛定(P<0.05)。(2)钙剂组大鼠脊髓背角神经元中P2X3受体的表达显著低于吗啡及安痛定组;P物质在三组实验大鼠脊髓背角神经元、神经胶质细胞的表达均为阴性;钙剂和安痛定相比于吗啡抑制CGRP表达的作用更强。结论:在不同毒素浓度和不同时间下,钙剂和吗啡、安痛定的镇痛效果各有优劣,钙剂通过抑制P2X3受体及CGRP的表达进而抑制疼痛的作用较吗啡及安痛定更强,三种镇痛药物均可抑制P物质的表达。

Objective：To investigate the effect of calcium gluconate,morphine,antondine pre-emptive injection on the behaviors and expression of pronociceptive mediators of rats poisoned by latrodectus tredecimguttatus spiders＇ toxin.Methods：One hundred and twenty male SD rats were divided into three groups randomly：calcium group,morphine group and antondine group,of which each rat was received injection of analgesic drug before injection of different concentrations of latrodectus tredecimguttatus spiders＇ toxin.The nociceptive response and flinching time were observed and recorded.The expression of pronociceptive mediators,including P2X3 receptors,SP,CGRP,in spinal cord were detected by immunohistochemistry.Results：（1） When the toxin concentration is 10 μl/kg,the analgesic effect of morphine is stronger than that of antondine and the calcium group is the worst at 15 min.However,at 30 min the effect of morphine and antondine are superior to the effect of themselves at 15 min,while the effect of calcium is the best.When the concentration is 300 μl/kg,the analgesic effect of calcium is much stronger than that of morphine and antondine.（2） The expression of P2X3 receptors of calcium group was lower than that of morphine and antondine group prominently.The expression of SP in all of three groups is feminine in the spinal cord.The inhibition of CGRP by calcium and antondine are superior to morphine.Conclusions：The analgesic effect of calcium,morphine and antondine has their advantages at different concentration and time.The inhibition of P2X3 receptors and CGRP by calcium to relieve pain is more powerful than morphine and antondine.All three kinds of analgesic drugs could eliminate the expression of SP.