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身痛逐瘀颗粒对偏头痛大鼠的作用及MAPK信号通路的影响

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目的 探讨身痛逐瘀颗粒(SZK)对偏头痛大鼠的镇痛作用及丝裂原活化蛋白激酶(MAPK)信号通路的影响。方法 将60只SD大鼠随机分为对照组,模型组,SZK低、中、高剂量组,卡马西平组,除对照组外均采用青霉素G钾建立偏头痛大鼠模型。观察SZK对偏头痛大鼠疼痛潜伏时间、疼痛反应次数及持续时间的影响;ELISA测定脑组织中5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)、大鼠内皮素-1(ET-1)水平;Western blot检测细胞外调节蛋白激酶(ERK)、磷酸化细胞外调节蛋白激酶(p-ERK)、P38丝裂原活化蛋白激酶(P38MAPK)、磷酸化P38丝裂原活化蛋白激酶(p-P38MAPK)、c-Jun氨基末端激酶(JNK)、磷酸化-氨基末端激酶(p-JNK)、甘油醛-3-磷酸脱氢酶(GAPDH)蛋白表达水平。结果 与模型组比较,SZK组及卡马西平组大鼠疼痛潜伏时间显著延长,自主及诱发疼痛次数显著减少,自主及诱发疼痛持续时间显著缩短,差异有统计学意义(P<0。05);与模型组比较,SZK高剂量组及卡马西平组大鼠自主疼痛持续时间显著缩短,差异有统计学意义(P<0。05)。与模型组比较,SZK低、中、高剂量组及卡马西平组5-HT、NE、DA含量显著高于模型组,ET-1含量显著低于模型组,差异有统计学意义(P<0。05)。与模型组比较,SZK中、高剂量组偏头痛大鼠脑组织p-ERK、p-JNK、p-P38MAPK和P38MAPK蛋白表达显著增加,SZK低剂量组p-JNK和P38MAPK蛋白表达显著增加,卡马西平组P38MAPK蛋白表达显著增加,差异有统计学意义(P<0。05)。结论 SZK通过升高MAPK信号通路p-JNK、p-ERK、p-P38MAPK、P38MAPK蛋白表达水平来抑制青霉素G钾诱导的大鼠偏头痛症状。
Effect of Shentong Zhuyu Keli on migraine rats and its influence on MAPK signal pathway
Objective To investigate the analgesic effect of Shentong Zhuyu Keli(SZK)on migraine rats and its influence on mitogen-activated protein kinase(MAPK)signaling pathway.Methods A total of 60 SD rats were randomly divided into the control group,the model group,the low-,medium-and high-dose SZK groups and the carbamazepine group.Except for the control group,the migraine rat model was established by penicillin G potassium for all groups.The effect of SZK on the pain latency time,the number of pain reactions and the pain duration of migraine rats was observed.the levels of 5-hydroxy ryptamine(5-HT),norepinephrine(NE),dopamine(DA)and endothelin-1(ET-1)in brain tissue were measured by ELISA.Western blot was adopted to detect the protein expression levels of extracellular signal regulated-kinase(ERK),phosphorylated extracellular regulatory protein kinase(p-ERK),P38 mitogen-activated protein kinase(P38MAPK),phosphorylated P38 mitogen-activated protein kinase(p-P38MAPK),c-Jun N-terminal kinase(JNK),phosphorylated c-Jun N-terminal kinase(p-JNK),and glyceraldehyde-3-phosphate dehydrogenase(GAPDH).Results Compared with the model group,the pain latency time in the SZK groups and the carbamazepine group was significantly prolonged,the number of spontaneous and induced pain decreased significantly,and the duration of spontaneous and induced pain was significantly shortened,with statistically significant differences(P<0.05).compared with the model group,the duration of spontaneous pain in the high-dose SZK group and the carbamazepine group was significantly shortened,with statistically significant difference(P<0.05).Compared with the model group,the levels of 5-HT,NE and DA in the low-,medium-and high-dose SZK groups and the carbamazepine group were significantly higher,and the level of ET-1 was significantly lower,with statistically significant differences(P<0.05).Compared with the model group,the expression levels of p-ERK,p-JNK,p-P38MAPK and P38MAPK in the brain tissue of migraine rats in the middle-and high-dose SZK groups increased significantly,the expression levels of p-JNK and P38MAPK in the low-dose SZK group increased significantly,and the expression level of P38MAPK in the carbamazepine group increased significantly,with statistically significant differences(P<0.05).Conclusion SZK can inhibit the migraine symptoms induced by penicillin G potassium in rats by increasing the protein expression levels of p-JNK,p-ERK,p-P38MAPK and P38MAPK in MAPK signaling pathway.

Shentong Zhuyu KeliMigraine5-hydroxytryptamineNorepinephrineDopamineMitogen-activated protein kinase pathway

王珑、赵静、刘小军、苗倩倩、朱露

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西安新润药业有限公司药物研发中心,陕西西安 710003

身痛逐瘀颗粒 偏头痛 5-羟色胺 去甲肾上腺素 多巴胺 丝裂原活化蛋白激酶通路

陕西省2020年科技计划项目

2020ZDLSF05-12

2024

中国医药科学
海峡两岸医药卫生交流协会 二十一世纪联合创新(北京)医药科学研究院

中国医药科学

影响因子:1.083
ISSN:2095-0616
年,卷(期):2024.14(8)
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