头痛宁胶囊对偏头痛大鼠BDNF/TrkB信号通路表达的影响

目的观察头痛宁胶囊对偏头痛大鼠模型中脑源性神经营养因子(BDNF)及其信号通路上酪氨酸激酶(TrkB)受体、下游信号分子细胞外调节蛋白激酶(ERK)、磷酸化cAMP反应结合蛋白(p-CREB)表达的影响。方法将60只SD大鼠随机分为正常对照组、模型组、头痛宁干预组,依照Tassorelli法建立硝酸甘油实验性偏头痛SD大鼠模型,观察各组大鼠的行为学变化,第五次建模后用ELISA法检测血清BDNF水平及免疫组化法检测三叉神经组织中BDNF、TrkB受体、下游信号分子ERK和p-CREB的蛋白表达变化及其定位。结果行为学观察结果显示:模型组及干预组大鼠造模后出现挠头增多、双耳发红、爬笼活动频繁,但干预组大鼠的持续时间及挠头爬笼次数较模型组减少,差异具有统计学意义(P<0.05);对照组未出现上述行为学改变。ELISA结果显示:模型组大鼠发作期及间歇期血清BDNF水平高于干预组发作期及间歇期和对照组(P<0.05),无性别差异(P>0.05)。免疫组化结果显示:模型组大鼠发作期三叉神经节细胞内BDNF、TrkB、p-ERK、p-CREB的蛋白水平高于干预组发作期及间歇期和对照组(P<0.05),无性别差异(P>0.05)。结论头痛宁胶囊可能通过下调BDNF、TrkB、p-ERK、p-CREB蛋白的表达水平来达到防治偏头痛的作用。

Effect of Toutongning Capsule on BDNF/TrkB signaling pathway in rats with migraine

Objective To investigate the effect of Toutongning Capsule on brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB) receptor, extracellular signal-regulated kinase (ERK), and phosphorylated cAMP-response element binding protein (p-CREB) in rats with migraine. Methods A total of 60 Sprague-Dawley (SD) rats were randomly divided into control group, model group, and Toutongning intervention group. Nitroglycerin-induced SD rat models of migraine were established using the Tassorelli Methods The behavioral changes of the rats were observed. After the fifth time of establishment of rat models, ELISA was used to measure BDNF level, and immunohistochemistry was used to detect the protein expression and localization of BDNF, TrkB, ERK, and p-CREB in the trigeminal ganglion of the rats.Results Ethological observation showed that rats in the model group and intervention group scratched their heads and climbed the cage frequently and had red ears, with the intervention group having a shorter duration and lower frequencies of scratching heads and climbing cage compared with the model group (P<0.05). The control group did not show the above behavioral changes. ELISA results showed that the model group had a higher serum BDNF level in the ictal and interictal periods than that of the intervention group in the same periods and that of the control group (P<0.05), showing no gender difference (P>0.05). Immunohistochemistry results showed that the model group had higher protein levels of BDNF, TrkB, p-ERK, and p-CREB in the trigeminal ganglion in the ictal and interictal periods than those of the intervention group in the same periods and those of the control group (P<0.05), showing no gender difference as well. (P>0.05).Conclusions Toutongning Capsule can prevent migraine through down-regulating the protein expression of BDNF, TrkB, ERK, and p-CREB.