【摘要】：偏頭痛(migraine)是一種常見的神經(jīng)系統(tǒng)疾病,因其發(fā)病率高,反復(fù)發(fā)作,發(fā)作時(shí)疼痛劇烈,遷延難愈等特點(diǎn),給患者造成極大的痛苦,并且與腦梗死、抑郁癥等多種疾病密切相關(guān),嚴(yán)重影響著人類的健康。因此,偏頭痛的防治是醫(yī)學(xué)研究的重要課題。中醫(yī)藥從整體觀念出發(fā)進(jìn)行辨證論治,治療偏頭痛具有自身的優(yōu)勢與特點(diǎn)。然而由于基礎(chǔ)研究相對薄弱,限制了中醫(yī)藥防治偏頭痛優(yōu)勢的發(fā)揮,因此將傳統(tǒng)中醫(yī)學(xué)理論與現(xiàn)代醫(yī)學(xué)前沿相結(jié)合,進(jìn)一步研究中醫(yī)藥防治偏頭痛的深層機(jī)制,為中醫(yī)藥防治偏頭痛提供新的證據(jù)支持,對中醫(yī)藥更好地發(fā)展與更廣泛的傳播具有重要意義。研究目的:1.探索偏頭痛大鼠不同時(shí)間節(jié)點(diǎn)三叉神經(jīng)頸復(fù)合體(trigeminal cervical complex,TCC)內(nèi)PPARs各亞型的表達(dá)情況,分析PPARs各亞型表達(dá)的相對高峰時(shí)間。2.研究中成藥天舒膠囊對偏頭痛大鼠TCC內(nèi)PPARs各亞型表達(dá)的影響,比較天舒膠囊和PPARs激動劑(GW0742)干預(yù)后大鼠血漿中CGRP的變化,進(jìn)一步闡述天舒膠囊治療偏頭痛的作用機(jī)制。研究方法:實(shí)驗(yàn)一 不同時(shí)間節(jié)點(diǎn)偏頭痛大鼠TCC內(nèi)PPARs各亞型的表達(dá)1.24只SD大鼠分為模型組和空白組,空白組正常飼養(yǎng),模型組給予皮下注射硝酸甘油的方法造模。2.造模后持續(xù)錄像2小時(shí),觀察大鼠行為學(xué)變化。3.造模后2小時(shí)空白組和模型組各取6只大鼠,麻醉后斷頭取腦組織,造模后4小時(shí),同樣方法取剩余大鼠腦組織。4.免疫組化法觀察PPARs各亞型在TCC中的表達(dá)。實(shí)驗(yàn)二 天舒膠囊對PPARs各亞型表達(dá)的調(diào)控研究1.32只大鼠分為4組,空白組(正常飼養(yǎng),不給任何處理),模型組(生理鹽水灌胃7天后,給予造模),天舒膠囊組(天舒膠囊水溶液灌胃7天后,給予造模),GW0742組(生理鹽水灌胃7天后,腹腔注射GW0742,半小時(shí)后給予造模)。2.造模后給予錄像2小時(shí)觀察行為學(xué)變化。3.造模后4小時(shí)腹主動脈取血,斷頭取腦組織。4.ELISA法檢測血漿中CGRP含量,免疫組化法檢測PPARs各亞型在TCC中的表達(dá)。研究結(jié)果:1.PPARα在偏頭痛大鼠TCC內(nèi)表達(dá)趨勢是先降低后升高;PPARβ在偏頭痛大鼠TCC中的表達(dá)趨勢在4小時(shí)內(nèi)持續(xù)升高;PPARy在偏頭痛大鼠TCC中的表達(dá)趨勢是先升高后回降至正常。2.天舒膠囊和GW0742均可以降低偏頭痛大鼠的行為學(xué)評分,進(jìn)而用來治療偏頭痛。3.天舒膠囊可以增加PPARα、PPARβ在偏頭痛大鼠TCC中的表達(dá),而對PPARγ的表達(dá)無影響;GW0742可以增加PPARβ在TCC中的表達(dá),抑制PPARα的表達(dá),對PPARγ表達(dá)無影響。4.天舒膠囊和GW0742均可以降低偏頭痛模型大鼠血漿中CGRP的水平。結(jié)論意義:1.天舒膠囊對防止偏頭痛的發(fā)生有一定的積極作用。2.天舒膠囊可以通過激活偏頭痛大鼠模型TCC內(nèi)PPARα、PPARβ的表達(dá)以及降低血漿中CGRP的水平來達(dá)到防止偏頭痛發(fā)生的目的。3.天舒膠囊有類似于PPAR β激動劑的效果來激活PPARβ進(jìn)而防止偏頭痛的發(fā)生,但是其作用效果與PPARβ激動劑有所不同。4.PPARs可能是未來中藥防治偏頭痛的一個(gè)新的靶點(diǎn)。
[Abstract]:Migraine (migraine) is a common nervous system disease. Because of its high incidence, recurrent attacks, severe pain and difficult to recover, it causes great pain and is closely related to many diseases such as cerebral infarction and depression, which seriously affect human health. Therefore, the prevention and control of migraine is important in medical research. Chinese medicine has its own advantages and characteristics in treating migraine from the whole concept. However, because the basic research is relatively weak, it restricts the exertion of the advantage of the prevention of migraine in traditional Chinese medicine. Therefore, the traditional Chinese medicine theory is combined with the frontier of modern medicine to further study the deep level of the prevention of migraine in traditional Chinese medicine. The mechanism provides new evidence support for the prevention and control of migraine in traditional Chinese medicine. It is of great significance to the better development and wider spread of traditional Chinese medicine. 1. to explore the expression of PPARs subtypes in trigeminal cervical complex (TCC) in different time nodes of migraine rats, and to analyze the expression of each subtype of PPARs. The relative peak time.2. study on the effect of Chinese medicine Tianshu Capsule on the expression of PPARs subtypes in TCC of migraine rats, compared the changes of CGRP in the plasma of rats after the intervention of Tianshu capsule and PPARs agonist (GW0742), and further elaborated the mechanism of the action of Tianshu capsule in the treatment of migraine. The research method: the experiment of a different time node migraine rat TC The expression of each subtype of C PPARs in 1.24 SD rats was divided into model group and blank group, the blank group was raised normally, and the model group was given a method of subcutaneous injection of nitroglycerin for 2 hours after making models of the model group and observed the behavior changes of the rats after the.3. model and the 2 hour blank group and the model group. After the anesthesia, the brain tissue was taken out of the head and the model was made after the anesthesia. 4 hours, the same method was used to observe the expression of PPARs subtypes in TCC by using.4. immunohistochemistry in the remaining rat brain tissue. Experimental two Tianshu capsule was used to regulate the expression of PPARs subtypes. 1.32 rats were divided into 4 groups, the blank group (normal feeding, no treatment), the model group (7 days after gavage of raw saline), Tianshu capsule group (day) The water solution of Shu Capsule was given 7 days after gastric perfusion. Group GW0742 (7 days after gastric perfusion, intraperitoneal injection of GW0742, half an hour after being given model),.2. was given a video for 2 hours to observe behavioral changes and observe behavioral changes in the abdominal aorta for 4 hours after 2 hours. The content of CGRP in plasma was detected by.4.ELISA method of brain tissue, and PPARs was detected by immunohistochemical method for PPARs. The expression of each subtype in TCC: the expression trend of 1.PPAR alpha in migraine rats was first decreased and then increased; the expression trend of PPAR beta in TCC of migraine rats increased continuously in 4 hours, and the expression trend of PPARy in TCC in migraine rats was first increased and then descended to normal.2. Tianshu capsule and GW0742 to reduce the bias. The behavior score of the pain rats, and then used to treat migraine.3. Tianshu capsule can increase the expression of PPAR a, PPAR beta in the TCC of migraine rats, but no influence on the expression of PPAR gamma; GW0742 can increase the expression of PPAR beta in TCC, inhibit the expression of PPAR alpha, and do not affect the expression of.4. Tianshu capsule and GW0742 to reduce migraine. The level of CGRP in plasma of rat model. Conclusion: 1. Tianshu capsule has a positive effect on preventing migraine..2. Tianshu capsule can be activated by activating PPAR alpha in TCC of migraine rat model, expression of PPAR beta and reducing the level of CGRP in plasma to prevent migraine from occurrence of migraine,.3. Tianshu capsule is similar to PPAR The effect of beta agonist activates PPAR beta and then prevents migraine, but its effect is different from that of PPAR beta agonist,.4.PPARs may be a new target for the prevention and treatment of migraine in the future.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R285.5

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