弩药液的镇痛作用及对炎性疼痛因子TNF-α、IL-6和PGE2的影响

Analgesic Effect of Crossbow Liquid and its Effect on Inflammatory Pain Factors TNF-α,IL-6 and PGE2

目的:研究苗药制剂弩药液的镇痛作用及作用机制,为弩药液的临床应用提供药理学基础。方法:采用小鼠热板实验,雄性ICR小鼠40只,随机分为模型组,弩药液高、中、低剂量组,每组10只,连续7 d腹部涂抹给药后测定末次给药后小鼠30 min、60 min、90 min痛阈值;采用小鼠扭体实验,ICR小鼠50只,雌雄各半,随机分为模型组,弩药液高、中、低剂量组,纳络酮+高剂量组,每组10只,连续7 d腹部涂抹给药后腹腔注射0.8%冰醋酸生理盐水溶液,随即记录小鼠扭体潜伏期和15 min内扭体次数;采用大鼠福尔马林致痛实验,SD大鼠30只,雌雄各半,随机分为空白组,模型组,弩药液高、中、低剂量组,每组6只,连续7 d腹部涂抹给药后于大鼠右足底皮下注射5%福尔马林生理盐水溶液,随即记录大鼠第一时相和第二时相舔咬后足持续时间,并且检测大鼠血清炎性疼痛因子TNF-α、IL-6和PGE2浓度。结果:热板实验中,小鼠给药后30 min和60 min高剂量组与模型组以及高剂量组给药后60 min和90 min与给药后30 min痛阈值比较,均有显著性差异(P<0.05);扭体实验中,模型组、低剂量组及纳络酮+高剂量组与高剂量组潜伏期及扭体次数比较均有显著性差异(P<0.05);福尔马林致痛实验中,各组大鼠舔咬后足持续时间第一时相无显著性差异(P>0.05),高、中剂量组与模型组舔咬后足持续时间第二时相比较,有显著性差异(P<0.05),空白组、高剂量组和中剂量组大鼠血清IL-6、PGE2浓度均与模型组比较,有显著性差异(P<0.05),空白组血清TNF-α浓度与模型组比较,有显著性差异(P<0.05),给药组血清TNF-α浓度较模型组有所降低,但无显著性差异(P>0.05)。结论:弩药液对多种疼痛模型具有显著镇痛作用,可能作用于阿片类受体,作用机制可能与显著下调炎性疼痛因子IL-6、PGE2有关。

Objective To study the analgesic effect and possible mechanism of Nuyaoye,miao medicine preparation,to provide pharmacological basis for clinical application of Nuyaoye.Methods Forty Female ICR mice were randomly divided into model group,high-dose,medium-dose and low-dose groups with 10 mice in each group.The pain threshold of 30 min,60 min and 90 min after the last administration was measured after 7 days of abdominal smear.A total of 50 ICR mice(Male and female half)were randomly divided into model group,high-dose,medium-dose and low-dose naloxone+high-dose groups,with 10 mice in each group.After 7 days of abdominal administration,0.8% glacial acetic acid normal saline solution was intraperitoneally injected.The latency period of writhing and the number of writhing within 15 minutes were recorded.Using rats foer Ma Linzhi pain experiment,30 SD rats(Male and female half)were randomly divided into blank group,model group,crossbows,solution of high,middle,low dose group,each group of six,seven d rats after abdominal daub to right plantar subcutaneous injection of 5% formalin saline solution,then record first and 2 in the first phase of rats lick bite after sufficient duration,Serum concentrations of inflammatory pain factors TNF-α,IL-6 and PGE2 were detected.Results In the hot plate experiment,there were significant differences between the pain threshold of the high-dose group and the model group 30min and 60min after administration,and the pain threshold of the high-dose group 60min and 90min after administration and 30min after administration(P<0.05).In the writhing experiment,there were significant differences in latency and writhing times between the model group,low-dose group,naloxone+high-dose group and high-dose group(P<0.05).In the formalin-induced pain experiment,there was no significant difference in the first phase of the licking hind foot duration among all groups(P>0.05),but there was a significant difference in the second phase of the licking hind foot duration between the high-dose and medium-dose groups and the model group(P<0.05).The serum concentrations of IL-6 and PGE2 in blank group,high-dose group and medium-dose group were significantly different from those in model group(P<0.05).The serum concentrations of TNF-α in blank group were significantly different from those in model group(P<0.05).The serum concentrations of TNF-α in administration group were decreased compared with that in model group,but there was no significant difference(P>0.05).Conclusion The miaoyao preparation Nuyaoye has significant analgesic effects on various pain models,which may act on opioid receptors,and the mechanism of action may be related to the significant down-regulation of inflammatory pain factors IL-6 and PGE2.