Objective: To evaluate the effects of Xiongzhi Dilong decoction(XZDLD) and its wind medicine on calcitonin gene-related peptide(CGRP)-induced migraine and explore the mechanism through the CGRP/inducible nitric oxide ...Objective: To evaluate the effects of Xiongzhi Dilong decoction(XZDLD) and its wind medicine on calcitonin gene-related peptide(CGRP)-induced migraine and explore the mechanism through the CGRP/inducible nitric oxide synthase(iNOS) pathway.Methods: Rats were divided into control, model, XZDLD, XZDLD(external wind), XZDLD(internal wind),and olcegepant groups. CGRP was injected into the dura mater to induce a migraine. The frequency of head scratching, cage climbing, and facial grooming was observed. The pain threshold, the levels of CGRP,pituitary adenylate cyclase activating polypeptide(PACAP), substance P(SP), and the plasma protein extravasation(PPE) ratio were measured. The phosphorylation levels of p38, extracellular signalregulated kinase 1/2(ERK1/2), and expression of iNOS were detected by western blot.Results: Compared with the model group, the three modified XZDLD groups showed reduced frequency of head scratching and cage climbing in the first 30 min(all P <.05). Facial grooming frequency was reduced in XZDLD and XZDLD(external wind) groups(P =.0003 and P =.0131, respectively). External wind medicine played a more important role in increasing mechanical pain threshold than internal wind medicine. Moreover, compared with the model group, the three modified XZDLD groups demonstrated reduced plasma levels of CGRP and PACAP(all P <.05). No difference in the SP level was observed among the six groups. XZDLD reduced PPE ratio. XZDLD and XZDLD(external wind) groups suppressed the CGRP/iNOS pathway by inhibiting the p-p38/p38 ratio and the expression of iNOS. No difference in pERK1/2/ERK1/2 ratio was detected among the six groups.Conclusion: XZDLD increases pain threshold, downregulates the expression of CGRP and PACAP, and reduces PPE ratio by inhibiting the CGRP/iNOS pathway. External wind medicine is more effective than internal one on improving facial grooming and head scratching, increasing the mechanical pain threshold, and inhibiting the expression of iNOS.展开更多
目的:研究芎芷地龙汤不同时间预给药对偏头痛动物模型痛阈及血管活性物质的影响。方法:将健康雄性SD大鼠,随机分为生理盐水组、模型组、舒马普坦组、中药治疗组,每组8只,给药干预后,皮下注射硝酸甘油注射剂10 mg/kg制作偏头痛动物模型,...目的:研究芎芷地龙汤不同时间预给药对偏头痛动物模型痛阈及血管活性物质的影响。方法:将健康雄性SD大鼠,随机分为生理盐水组、模型组、舒马普坦组、中药治疗组,每组8只,给药干预后,皮下注射硝酸甘油注射剂10 mg/kg制作偏头痛动物模型,在皮下注射药物后2 h后测定,电子式机械测痛仪测定机械痛阈值,温度刺激仪测定温度痛阈值;硝酸还原法进行测定血浆NO浓度;ELISA法测定血浆CGRP、Neurokinin A、Endothelin-1(ET-1)、TXB2、6-Keto-PGF1α含量。结果:给予硝酸甘油后,模型组与生理盐水组比较,机械痛阈(1 d P<0.01,3 d P<0.05,7 d P<0.05)和温度痛阈(1 d P<0.01,3 d P<0.01,7 d P<0.01)均降低,血浆NO浓度升高(1 d P<0.01,3 d P<0.01,7 d P<0.01),血浆ET-1浓度降低(1 d P<0.05,3 d P<0.05,7 d P<0.01),血浆CGRP含量降低(1 d P<0.01,3 d P<0.01,7 d P<0.05),血浆NKA含量升高(1 d P<0.01,3 d P<0.01,7 d P<0.01),血浆TXB2含量降低(1 d P<0.01,3 d P<0.01,7 d P<0.05),血浆6-Keto-PGF1α含量降低(1 d P<0.05,3 d P<0.05,7 d P<0.01);预防给药后,芎芷地龙汤组和模型组比较,机械痛阈和温度痛阈均显著升高(3d P<0.01,7d P<0.05),NO浓度显著降低(3 d P<0.01,7 d P<0.01),血浆ET-1浓度升高(3 d P<0.01,7 d P<0.05),血浆CGRP浓度升高(7d P<0.01),NKA含量有所降低(1 d P<0.05,3 d P<0.05,7 d P<0.01),血浆TXB2含量有所增高(3d P<0.05,7 d P<0.01),血浆6-KetoPGF1α有所增高(3d P<0.05,7 d P<0.05)。结论:预防给药3天、7天,芎芷地龙汤均可以提高动物病理状态下的痛阈值,可减弱由NTG诱发的NO的升高水平,可升高由NTG诱发的TXB2降低水平,缓解由NTG诱发的6-Keto-PGF1α的降低水平,升高由NTG诱发的ET-1含量降低水平,减弱由NTG诱发的NKA的释放水平;预防给药7天后,芎芷地龙汤可以升高由NTG诱发的血浆CGRP降低水平。整体来分析,预防给药7天效果好于预防给药3天、1天。展开更多
基金funded by the National Natural Science Foundation of China (81873256)the National Key R&D Program of China “Study on Modernization of Traditional Chinese Medicine”(2019YFC1709702)。
文摘Objective: To evaluate the effects of Xiongzhi Dilong decoction(XZDLD) and its wind medicine on calcitonin gene-related peptide(CGRP)-induced migraine and explore the mechanism through the CGRP/inducible nitric oxide synthase(iNOS) pathway.Methods: Rats were divided into control, model, XZDLD, XZDLD(external wind), XZDLD(internal wind),and olcegepant groups. CGRP was injected into the dura mater to induce a migraine. The frequency of head scratching, cage climbing, and facial grooming was observed. The pain threshold, the levels of CGRP,pituitary adenylate cyclase activating polypeptide(PACAP), substance P(SP), and the plasma protein extravasation(PPE) ratio were measured. The phosphorylation levels of p38, extracellular signalregulated kinase 1/2(ERK1/2), and expression of iNOS were detected by western blot.Results: Compared with the model group, the three modified XZDLD groups showed reduced frequency of head scratching and cage climbing in the first 30 min(all P <.05). Facial grooming frequency was reduced in XZDLD and XZDLD(external wind) groups(P =.0003 and P =.0131, respectively). External wind medicine played a more important role in increasing mechanical pain threshold than internal wind medicine. Moreover, compared with the model group, the three modified XZDLD groups demonstrated reduced plasma levels of CGRP and PACAP(all P <.05). No difference in the SP level was observed among the six groups. XZDLD reduced PPE ratio. XZDLD and XZDLD(external wind) groups suppressed the CGRP/iNOS pathway by inhibiting the p-p38/p38 ratio and the expression of iNOS. No difference in pERK1/2/ERK1/2 ratio was detected among the six groups.Conclusion: XZDLD increases pain threshold, downregulates the expression of CGRP and PACAP, and reduces PPE ratio by inhibiting the CGRP/iNOS pathway. External wind medicine is more effective than internal one on improving facial grooming and head scratching, increasing the mechanical pain threshold, and inhibiting the expression of iNOS.
文摘目的:研究芎芷地龙汤不同时间预给药对偏头痛动物模型痛阈及血管活性物质的影响。方法:将健康雄性SD大鼠,随机分为生理盐水组、模型组、舒马普坦组、中药治疗组,每组8只,给药干预后,皮下注射硝酸甘油注射剂10 mg/kg制作偏头痛动物模型,在皮下注射药物后2 h后测定,电子式机械测痛仪测定机械痛阈值,温度刺激仪测定温度痛阈值;硝酸还原法进行测定血浆NO浓度;ELISA法测定血浆CGRP、Neurokinin A、Endothelin-1(ET-1)、TXB2、6-Keto-PGF1α含量。结果:给予硝酸甘油后,模型组与生理盐水组比较,机械痛阈(1 d P<0.01,3 d P<0.05,7 d P<0.05)和温度痛阈(1 d P<0.01,3 d P<0.01,7 d P<0.01)均降低,血浆NO浓度升高(1 d P<0.01,3 d P<0.01,7 d P<0.01),血浆ET-1浓度降低(1 d P<0.05,3 d P<0.05,7 d P<0.01),血浆CGRP含量降低(1 d P<0.01,3 d P<0.01,7 d P<0.05),血浆NKA含量升高(1 d P<0.01,3 d P<0.01,7 d P<0.01),血浆TXB2含量降低(1 d P<0.01,3 d P<0.01,7 d P<0.05),血浆6-Keto-PGF1α含量降低(1 d P<0.05,3 d P<0.05,7 d P<0.01);预防给药后,芎芷地龙汤组和模型组比较,机械痛阈和温度痛阈均显著升高(3d P<0.01,7d P<0.05),NO浓度显著降低(3 d P<0.01,7 d P<0.01),血浆ET-1浓度升高(3 d P<0.01,7 d P<0.05),血浆CGRP浓度升高(7d P<0.01),NKA含量有所降低(1 d P<0.05,3 d P<0.05,7 d P<0.01),血浆TXB2含量有所增高(3d P<0.05,7 d P<0.01),血浆6-KetoPGF1α有所增高(3d P<0.05,7 d P<0.05)。结论:预防给药3天、7天,芎芷地龙汤均可以提高动物病理状态下的痛阈值,可减弱由NTG诱发的NO的升高水平,可升高由NTG诱发的TXB2降低水平,缓解由NTG诱发的6-Keto-PGF1α的降低水平,升高由NTG诱发的ET-1含量降低水平,减弱由NTG诱发的NKA的释放水平;预防给药7天后,芎芷地龙汤可以升高由NTG诱发的血浆CGRP降低水平。整体来分析,预防给药7天效果好于预防给药3天、1天。
