c-Jun氨基末端激酶信号通路参与电刺激大鼠三叉神经节偏头痛模型降钙素基因相关肽表达调控

The mechanism of c-Jun N-terminal kinase signaling transduction pathway in calcitonin gene-related peptide of rat migraine model via stimulating trigeminal ganglion by electrode

目的探究c-Jun氨基末端激酶(c-Jun N-Terminal Kinase,JNK)信号转导通路对电刺激大鼠三叉神经节(TG)偏头痛模型中降钙素基因相关肽(CGRP)表达调控的作用。方法成年雄性SD大鼠随机分为空白对照组、假手术组、模型组、DMSO+模型组、SP50+模型组、SP25+模型组。采用电刺激大鼠单侧TG制作偏头痛模型,选择JNK信号通路特异性阻滞剂SP600125为干预药物。观察偏头痛造模前后的行为学变化。各组大鼠处理后24h,Western blot检测TG中磷酸化JNK蛋白(p-JNK)和JNK蛋白表达量并计算磷酸化比率,免疫组织化学染色检测CGRP表达量。结果大鼠造模后前肢挠头次数增加、爬笼次数减少(P<0.05)。模型组、假手术组、DMSO+模型组、SP25+模型组大鼠TG内p-JNK比率较空白对照组明显升高(P<0.05);SP50+模型组TG内p-JNK比率较模型组、SP25+模型组明显降低(P<0.05);模型组TG内CGRP表达量较空白对照组、SP50+模型组明显升高(P<0.05);模型组刺激侧TG内CGRP表达量明显高于未刺激侧。结论电刺激大鼠单侧TG可使偏头痛急性发作过程中关键的神经血管活性肽CGRP表达升高,引发大鼠行为学变化,且JNK信号通路参与了TG内CGRP的表达调控过程。

Objective To explore the mechanism of c-Jun N-terminal kinase （JNK） signaling transduction pathway in calcitonin gene-rclatcd peptide （C（3RP） of rat trigeminal ganglion （T（3） migraine model. Methods We randomly divided adult male SD rats into control, sham-operation, model, DMSO＋model, SP50＋model, and SP25＋model groups. We built the rat migraine model by stimulating TG with electrode and chose SP600125 as the intervention drug. We observed the behavior changes of rats before and after the surgery. The expressions of p-JNK and JNK protein were detected by Western blot, and the expression of CGRP in TG was detected by immunohistochemistry. Results After the stimulation, the number of times of head scratching was significantly higher than before （P〈O. 05） while the number of times of cage climbing was significantly lower than before （P〈 0.05）. The ratio of p-JNK/JNK in TG was significantly higher in model, sham, DMSO＋model, and SP50＋model groups than in control group （P〈O. 05）, while the ratio in SP50＋model group was lower than that in model and SP25＋model groups （P〈0.05）. The expression of CGRP in TG was significantly higher in model group than in control and SP50＋model groups （P〈0.05）. Conclusion This rat migraine model can simulate the process of migraine attack, cause the model rats＇ behavioral change and activate JNK signaling pathway. JNK signaling pathway participates in the regulation of the expression of CGRP in TG.