發(fā)布時間：2018-03-22 09:37

  本文選題：偏頭痛　切入點(diǎn)：基于體素的形態(tài)學(xué)分析　出處：《中國人民解放軍醫(yī)學(xué)院》2017年博士論文　論文類型：學(xué)位論文

【摘要】：研究背景及目的偏頭痛是一種原發(fā)性頭痛,其發(fā)病機(jī)制尚不清楚。基于體素的形態(tài)學(xué)分析(VBM)可捕捉大腦結(jié)構(gòu)的微細(xì)改變,對于參與偏頭痛發(fā)病機(jī)制的大腦結(jié)構(gòu)的揭示起著重要的作用。目前關(guān)于VBM顯示結(jié)構(gòu)改變的組織學(xué)機(jī)制尚不清楚,因此對于偏頭痛患者VBM顯示的改變結(jié)果需謹(jǐn)慎解釋。本研究擬通過研究偏頭痛模型大鼠大腦VBM顯示結(jié)構(gòu)改變與組織學(xué)改變的相關(guān)性明確VBM改變的組織學(xué)機(jī)制,同時進(jìn)一步探索偏頭痛的發(fā)病機(jī)制。方法1.通過炎癥湯刺激清醒大鼠硬腦膜建立偏頭痛模型將60只Sprague Dawley大鼠隨機(jī)平均分配到10組:低頻炎癥湯刺激組(10μL炎癥湯,每四天一次,刺激3周)、高頻炎癥湯刺激組(10μL炎癥湯,每天一次,刺激3周)、低頻炎癥湯刺激恢復(fù)組(低頻炎癥湯刺激3周后停止刺激3周)、高頻炎癥湯刺激恢復(fù)組(高頻炎癥湯刺激3周后停止刺激3周)、長時間高頻炎癥湯刺激組(高頻炎癥湯刺激6周)以及相應(yīng)對照組(將10μL炎癥湯替換為10μL生理鹽水)。2.行為學(xué)觀察及機(jī)械痛閾值測定大鼠行為學(xué)在給藥前錄制15分鐘,給藥后錄制30分鐘,每4天錄制一次。靜止和休息行為時間通過Etho VisionXT動物跟蹤軟件獲得。面部理毛時間通過人工計(jì)時記錄。給藥前用Von-Frey纖維絲測定大鼠給藥同側(cè)眶周皮膚機(jī)械痛閾值。低頻炎癥湯刺激組與其對照組每四天測一次,高頻炎癥湯刺激組與其對照組隔天一次。3.磁共振數(shù)據(jù)采集以及VBM分析給藥3周、6周后使用7.0T超導(dǎo)磁共振機(jī)給予大鼠行T2核磁結(jié)構(gòu)像掃描(每組6只)。使用spmratIHEP工具包對數(shù)據(jù)進(jìn)行圖像預(yù)處理及分析。4.組織學(xué)分析大鼠完成磁共振掃描之后,每組隨機(jī)選取5只進(jìn)行經(jīng)心臟灌注取腦。采用免疫組化染色的方法標(biāo)記感興趣區(qū)域前額葉、中腦導(dǎo)水管周圍灰質(zhì)(PAG)、腦橋被蓋部和三叉神經(jīng)脊髓核尾部(Sp5C)的相關(guān)指標(biāo)NeuN、GFAP、Ibal、MBP、PLP的表達(dá)情況。結(jié)果1.偏頭痛模型大鼠炎癥湯刺激組較相應(yīng)對照組在給予藥物刺激后大鼠出現(xiàn)更長的靜止、休息時間和面部理毛時間,差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。從給藥后第三天開始,高頻炎癥湯刺激組大鼠眶周皮膚機(jī)械痛閾值較其對照組明顯下降,具有統(tǒng)計(jì)學(xué)意義(P0.05)。2. VBM結(jié)果以及其與免疫組化染色結(jié)果的相關(guān)性與對照組相比,低頻炎癥湯刺激組在延髓和腦橋出現(xiàn)白質(zhì)體積增加。高頻炎癥湯刺激組與對照組相比,白質(zhì)體積增高表現(xiàn)在前額葉、前邊緣葉、海馬和運(yùn)動皮層等區(qū)域。高頻炎癥湯刺激恢復(fù)組與對照組相比,白質(zhì)體積增高表現(xiàn)在基底節(jié)、胼胝體以及海馬等區(qū)域;丘腦、PAG、腦橋等區(qū)域出現(xiàn)灰質(zhì)體積增加,海馬區(qū)域灰質(zhì)體積下降。與對照組相比,長時間高頻炎癥湯刺激組在前額葉、胼胝體、海馬、丘腦等區(qū)域出現(xiàn)白質(zhì)體積增高;灰質(zhì)體積下降區(qū)域表現(xiàn)在胼胝體、基底節(jié)及感覺皮層,同時下丘腦灰質(zhì)體積增加。白質(zhì)體積的指標(biāo)變化與髓鞘形成及繼發(fā)性炎癥改變?nèi)缧∧z質(zhì)細(xì)胞增生和膠質(zhì)細(xì)胞增生相關(guān)。PLP在反映髓鞘病變較MBP更敏感。結(jié)論1. VBM可發(fā)現(xiàn)傳統(tǒng)T2加權(quán)像核磁不能發(fā)現(xiàn)的潛在病理改變結(jié)構(gòu)。偏頭痛模型大鼠中存在腦干尤其是三叉神經(jīng)傳導(dǎo)系統(tǒng)的結(jié)構(gòu)異常,同時大鼠出現(xiàn)的痛覺過敏可能與前額葉的結(jié)構(gòu)異常相關(guān)。2. VBM結(jié)構(gòu)改變與髓鞘形成及繼發(fā)性炎癥改變相關(guān)。膠質(zhì)細(xì)胞的活化和髓鞘異常與偏頭痛相關(guān)性疼痛的發(fā)病機(jī)制相關(guān)。3.偏頭痛患者VBM結(jié)構(gòu)改變可能是頭痛反復(fù)發(fā)作的結(jié)果,同時VBM顯示的異常結(jié)構(gòu)在偏頭痛的慢性化過程中發(fā)揮作用。
[Abstract]:Background and objective: migraine is a primary headache, its pathogenesis is still not clear. Voxel based morphometry (VBM) can capture the fine structure of the brain changes, plays an important role in revealing the brain structures involved in the pathogenesis of migraine. At present the VBM display on the histological structure change mechanism not clear, so for migraine patients with VBM show a change in results should be interpreted with caution. In this study the brain VBM study of migraine model rats showed clear correlation is VBM changes of structure change and organizational changes to the organization, and to further explore the pathogenesis of migraine. Methods 1. Decoction by inflammatory stimulation of the dura mater in conscious rats to establish migraine model 60 Sprague Dawley rats were randomly assigned to 10 groups: low inflammation soup stimulation group (10 L inflammation soup, once every four days for 3 weeks, high frequency stimulation) Inflammation soup stimulation group (10 L inflammation soup, once every 3 weeks, low frequency stimulation) inflammation stimulation recovery group (low inflammation soup soup stimulation for 3 weeks after the cessation of stimulation for 3 weeks), high-frequency stimulation recovery group (high inflammation soup soup to stimulate inflammation 3 weeks after the cessation of stimulation for 3 weeks), long time with high frequency Zhengtang stimulation group (high frequency stimulation of inflammation Decoction for 6 weeks) and control group (10 L 10 L to replace the inflammatory soup saline).2. behavior observation and mechanical pain threshold determination of rat behavior before administration recorded 15 minutes, 30 minutes after administration of recording, recording every 4 rest and rest days. Time by Etho VisionXT animal tracking software. Facial grooming time by manual timing records. Before administration of Von-Frey fiber was administered to rats ipsilateral periorbital skin mechanical pain threshold. The low frequency stimulation of inflammation Decoction group and the control group were measured once every four days, the high frequency stimulation of inflammation soup group and The control group next time.3. magnetic resonance data acquisition and analysis of VBM treatment for 3 weeks, 6 weeks after the use of 7.0T superconducting magnetic resonance machine was given to rats for T2 magnetic structure imaging (n = 6). After using the spmratIHEP toolkit for image preprocessing and analysis of.4. histological analysis of rats performed MRI scans on the data in each group, 5 rats were randomly selected from perfusion through the heart and brain. The immunohistochemical staining method of marker region of interest in prefrontal cortex, midbrain periaqueductal gray (PAG), pons tegmentum and trigeminal spinal nucleus (Sp5C) tail correlation index NeuN, GFAP, Ibal, MBP, PLP expression. Compared with the control group in the presence of longer static rats were given drugs to stimulate the inflammation after the decoction of 1. migraine model rats were stimulated, rest time and facial hair, the difference was statistically significant (P0.05). From the third day after administration, high frequency Inflammation soup stimulated rats periorbital skin mechanical pain threshold decreased significantly compared to the control group, with statistical significance (P0.05) and the.2. VBM results and immunohistochemical staining of the relevance of the results compared with the control group, the low frequency of inflammatory stimulation group in the medulla oblongata and pons Decoction appear white matter volume increased. High frequency stimulation group and inflammatory soup compared with the control group, the white matter volume increased in the prefrontal cortex, anterior limbic lobe, hippocampus and motor cortex area. High frequency stimulation to restore inflammation Decoction group compared with the control group, the white matter volume increased in the basal ganglia, hippocampus and corpus callosum region; the thalamus, PAG, pons area increased gray matter volume, hippocampus regional gray matter volume decreased. Compared with the control group, long time high frequency stimulation group inflammatory soup in the prefrontal cortex and corpus callosum, hippocampus, thalamus and other regions appear white matter volume increased; a decrease in gray matter volume area now corpus callosum, basal And the sensory cortex, and hypothalamus increased gray matter volume. Changes of white matter volume and myelin formation and secondary inflammatory changes such as proliferation of microglia and glial cell proliferation related.PLP in reflecting the myelin lesions were more sensitive than MBP. Conclusion: 1. VBM can be found in traditional T2 weighted images can not be found in nuclear magnetic potential pathological structural changes. Especially the brainstem trigeminal nerve conduction system abnormalities in migraine rats, abnormal structure and hyperalgesia may also appear in the prefrontal cortex of rats.2. VBM structure change and myelin formation and secondary inflammatory changes. Change the structure of VBM associated with the pathogenesis of.3. by activation of glial cells and myelin abnormalities and migraine related pain the recurrent headache migraine may be the result of abnormal structure at the same time VBM display play a role in the progress of chronic migraine.

【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R747.2;R-332

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