蜂毒穴位注射对偏头痛模型大鼠PKA、PACAP及c-Jun的影响  

The effects of bee venom acupoint injection on PKA,PACAP and c-Jun in migraine model rats

作　　者：杨花菊 刘思婷 徐峰 王亚飞 兰小路 李泽琼 王雅璇[1] 曹鑫怡 YANG Huaju;LIU Siting;XU Feng;WANG Yafei;LAN Xiaolu;LI Zeqiong;WANG Yaxuan;CAO Xinyi(Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学,100029 [2]北京中医药大学第三附属医院 [3]纽约大学

出　　处：《环球中医药》2021年第11期1951-1957,共7页Global Traditional Chinese Medicine

基　　金：北京中医药大学第三附属医院科研课题孵化项目(2019kyfh-07)。

摘　　要：目的研究蜂毒对急性偏头痛的治疗效果及相关机制。方法将48只大鼠分为正常对照组、偏头痛模型组、佐米曲普坦组、蜂毒高剂量组、蜂毒中剂量组、蜂毒低剂量组。正常对照组皮下注射生理盐水10 mg/kg,其余各组大鼠采用后颈部皮下注射硝酸甘油注射液10 mg/kg制备急性偏头痛模型。造模成功后,佐米曲普坦组于两侧太冲、合谷穴注射1 mg/kg生理盐水,同时给予佐米曲普坦1 mg/kg灌胃。正常对照组与偏头痛模型组分别于两侧太冲、合谷穴注射1 mg/kg生理盐水,同时给予佐米曲普坦组同等容量的生理盐水灌胃。蜂毒高、中、低剂量组分别于两侧太冲、合谷穴分别注射0.1 mg/kg、0.05 mg/kg、0.025 mg/kg蜂毒,同时给予佐米曲普坦组同等容量的生理盐水灌胃。用酶联免疫吸附测定法检测大鼠血浆中蛋白激酶A(protein kinase A,PKA)、垂体腺苷酸环化酶激活肽(pituitary adenylate cyclase-activating peptide,PACAP)含量;用蛋白质印迹法定量检测大鼠脑组织中原癌基因c-Jun的表达。结果(1)与正常对照组比较,偏头痛模型组的耳红开始时间明显缩短、挠头及爬笼次数和血浆中PKA、PACAP及脑组织的c-Jun蛋白表达有明显升高。(2)与偏头痛模型组比较,佐米曲普坦组、蜂毒高、中剂量组能明显降低大鼠血浆中PKA、PACAP和脑组织的c-Jun蛋白表达(P<0.01),蜂毒低剂量组只能明显降低PKA含量(P<0.01)。(3)与佐米曲普坦组比较,蜂毒高剂量组在0~60分钟的挠头次数、30~90分钟的爬笼次数、PKA 2小时含量、PACAP 2小时和4小时的含量差异不明显(P>0.05);而c-Jun表达差异性大,且蜂毒高剂量组表达低于佐米曲普坦组(P<0.01)。结论(1)高剂量的蜂毒可以明显改善偏头痛的症状。(2)蜂毒可能通过cAMP-PKA-CREB信号通路及其影响因子PACAP、c-Jun来参与偏头痛的发生发展。Objective To study the therapeutic effect of bee venom on acute migraine and its related mechanism.Methods 48 rats were randomly divided into 6 groups on average,including normal control group,migraine model group,zolmitriptan group,bee venom high-dose group,bee venom medium-dose group and bee venom low-dose group.Control group was subcutaneously injected with normal saline(10 mg/kg),and other groups were subcutaneously injected with nitroglycerin(10 mg/kg)in posterior neck to make an acute migraine rat model.The drug was administered 5 minutes after the model was successfully established.Zolmitriptan group was injected with 1 mg/kg normal saline acupuncture at Taichong and Hegu,and given 1 mg/kg zolmitriptan by intragastric gavage.Normal control group and migraine model group were injected with 1 mg/kg normal saline acupuncture at Taichong and Hegu,respectively,and the same volume of normal saline was given intragastric administration as zolmitroptan group.The high-dose,medium-dose and low-dose bee venom groups were injected with 0.1 mg/kg,0.05 mg/kg and 0.025 mg/kg bee venom acupuncture at Taichong and Hegu,respectively,and the same volume of normal saline was given intragastric administration as that of zolmetruptan group.After successful modeling,the starting and disappearing time of red ears and the time of scratching head and climbing cage of rats were observed.Plasma levels of protein kinase(PKA)and pituitary adenylate cyclase-activating peptide(PACAP)were determined by ELISA.The expression of c-Jun was quantitatively detected by Western blot.Results Compared with the normal control group,the values of model group were significantly increased.Compared with model group,zolmitraptan group,bee venom high-dose and medium-dose groups could significantly reduce the plasma levels of PKA,PACAP and c-Jun protein in brain tissue,while bee venom low-dose group could only significantly reduce the content of PKA.Compared with zolmitriptan group,bee venom high-dose group were not significantly different on the head scra

关 键 词：蜂毒 偏头痛 蛋白激酶A 垂体腺苷酸环化酶激活肽 C-JUN 

分 类 号：R285.5[医药卫生—中药学]