D-丝氨酸调节N-甲基-D-天冬氨酸受体在延髓背角参与偏头痛发病的机制研究

D- serine is a recently discovered co-agonist of NMDA receptor, proved to participate in a variety of neurological disorders such as epilepsy, motional dysfunction, cognitive injury and so on. It is reported that migraine is closely related with the diseases listed above. They are comorbid disorders, but the mechanism underlying is still unclear. The basic research part of the present study, basing on the previously established rat mode of migraine\chronic migraine\migraine with depression, is plan to use intracerebroventricular administration, ELISA, immunochemistry, immunofluorescent staining , Western blot and electrophysiology methods to investigate the role of D-serine on the migraine and NMDA receptor regulated by D-serine in the pathogenesis of migraine in the medullay dorsal horn; the clinical research part of the present study will compare the plasma level of D-serine/synthetic degrading enzymes/ glutamate in patients with and without migraine and control; observe the effect of orally taking D-serine on the frequency and extent of migraine in patients. The aim of the present study is to further elucidate the pathogenesis of migraine and its comorbidity and provide a theoretical basis for the drug treatment.

D-丝氨酸（D-serine）是一种新近发现的NMDA受体特别调控因子，被证明参与多种神经系统疾病的发生，如癫痫、情感障碍、认知损害等。偏头痛与上述疾病关系密切，是共患疾病，目前发病机制尚不明确。本研究的基础部分在前期建立的清醒状态下电刺激大鼠上矢状窦旁硬脑膜偏头痛模型、慢性偏头痛模型、偏头痛合并抑郁模型的基础上，采用行为学、ELISA、免疫荧光、免疫组化、Western blot、微透析、电生理等方法，明确D-serine对偏头痛大鼠的行为学影响、探索D-serine调节N-甲基-D-天冬氨酸受体（NMDAR）在延髓背角参与偏头痛发病的机制；临床研究部分将检测偏头痛患者发病和发病间期血浆内D-serine、合成酶、谷氨酸等物质的水平、明确服用D-serine对偏头痛发生频率和程度及情绪等方面的影响，从D-serine和NMDA受体角度进一步阐明偏头痛的发病机制、为药物治疗提供理论依据。

D-丝氨酸（D-serine）作为NMDA受体特别调控因子，参与多种神经系统疾病的发生。本研究采用免疫组化、药物-动物行为学、分子生物学等实验手段，采用前期建立的清醒状态下电刺激大鼠上矢状窦旁硬 脑膜偏头痛模型、慢性偏头痛模型、偏头痛合并抑郁大鼠模型，证明了D-丝氨酸参与偏头痛的发生和调节，通过增加脑脊液中D-丝氨酸的水平，可以减少上述大鼠模型中的伤害性行为。在动物模型中，延髓背角内D-丝氨酸的水平在给予电刺激时明显增高，丝氨酸消旋酶表达下降、NR2B受体无变化，并采用western blot方法，证明了上述免疫组化结果。因实验手段限制，偏头痛患者血及脑脊液中相应指标的检测及药物行为学观察未能如愿进行。从实验结果看，D-丝氨酸参与偏头痛的发病，对头痛有抑制效应，但其在延髓背角内表达增加、产生酶下降和作用受体无变化之间的矛盾结果，尚需进一步明确其可能的机制。