本文選題：蛋白激酶C + 慢性偏頭痛��； 參考：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景:偏頭痛是一種常見的原發(fā)性頭痛,具有反復(fù)發(fā)作的特點(diǎn),頭痛具有單側(cè)性、搏動性、程度中到重度、日�；顒蛹又氐忍攸c(diǎn),伴隨有惡心、嘔吐、畏光和畏聲等自主神經(jīng)癥狀。偏頭痛發(fā)病率較高,其反復(fù)發(fā)作嚴(yán)重影響患者的工作和生活質(zhì)量,給個(gè)人、家庭和社會帶來了嚴(yán)重的負(fù)擔(dān),已被WHO列為四大最嚴(yán)重的慢性功能障礙性疾病之一。偏頭痛根據(jù)其發(fā)作頻率可分為發(fā)作性偏頭痛(episodic migraine,EM)和慢性偏頭痛(chronic migraine,CM)。慢性偏頭痛的臨床診斷標(biāo)準(zhǔn)為:每月頭痛發(fā)作大于15天,持續(xù)三個(gè)月且無藥物濫用。慢性偏頭痛是偏頭痛常見的并發(fā)癥,每年大約有2.5%的發(fā)作性偏頭痛轉(zhuǎn)化為慢性偏頭痛。CM較EM給患者個(gè)人、家庭及社會帶來了更為嚴(yán)重的負(fù)擔(dān)。所以如何防止偏頭痛的慢性化是神經(jīng)病學(xué)領(lǐng)域的一重大難點(diǎn)。近年來,有許多研究發(fā)現(xiàn)在偏頭痛的慢性化中,中樞敏化扮演者重要角色,故進(jìn)一步研究偏頭痛的發(fā)中樞敏化機(jī)制,抑制偏頭痛的慢性化轉(zhuǎn)歸,是尋求偏頭痛新的治療靶點(diǎn)的重要方法,對于提高偏頭痛患者的生存質(zhì)量有著十分重要的意義。既往的研究發(fā)現(xiàn),在多種疼痛模型中,PKC活性顯著增高,而抑制PKC的活性后往往可以明顯減輕疼痛,提示PKC在疼痛的中樞敏化形成過程中發(fā)揮著重要作用。但是PKC是否參與慢性偏頭痛的中樞敏化機(jī)制,尚無相關(guān)研究報(bào)道,故本文旨在研究PKC是否通過中樞敏化參與慢性偏頭痛病理生理過程。方法:1、實(shí)驗(yàn)分組:SD雄性大鼠隨機(jī)分為7組。A、假手術(shù)組(n=11),硬膜外連續(xù)7天滴注PBS2μl。B、模型組(n=12),硬膜外連續(xù)7天滴注IS2μl。C、模型+溶劑組(n=8),硬膜外連續(xù)7天滴注IS2μl,側(cè)腦室注射DMSO5μl。D、PKC抑制劑低劑量組(n=11),硬膜外連續(xù)7天滴注IS2μl,側(cè)腦室注射CHE4μg(5μl)。E、PKC抑制劑高劑量組(n=10),硬膜外連續(xù)7天滴注IS2μl,側(cè)腦室注射CHE8μg(5μl)。F、PKC激動劑低劑量組(n=10),硬膜外連續(xù)7天滴注IS2μl,側(cè)腦室注射PMA100ng(5μl)。G、PKC激動劑高劑量組(n=11),硬膜外連續(xù)7天滴注IS2μl,側(cè)腦室注射PMA200ng(5μl)。2、硬膜外置管,手術(shù)后兩天,選擇傷口未感染,導(dǎo)管未堵塞的大鼠進(jìn)入下一步實(shí)驗(yàn)。給予IS或PBS緩慢硬腦膜外滴注,重復(fù)7天。模擬硬腦膜痛覺感受器的反復(fù)激活,建立慢性偏頭痛大鼠模型。3、慢性偏頭痛大鼠模型建立后,側(cè)腦室給予PKC抑制劑CHE和PKC激動劑PMA,使用Von Frey test測定大鼠面部及后足的機(jī)械痛閾值,Western blot和免疫熒光檢測TNC部位PKC、CGRP、c-Fos的蛋白的定位和表達(dá)變化。結(jié)果:1、“炎性湯”反復(fù)刺激硬腦膜后,大鼠面部及足底的機(jī)械痛閾值顯著降低,而三叉神經(jīng)脊束尾核部位的CGRP、c-Fos及PKC蛋白表達(dá)顯著增加。2、使用CHE抑制PKC可以顯著增高大鼠面部及足底痛閾值,顯著降低CGRP、c-Fos的表達(dá)。3、而使用PMA激活PKC則降低痛閾值,顯著增高CGRP、c-Fos的表達(dá)。結(jié)論:1、利用炎性湯反復(fù)刺激硬腦膜模擬大鼠慢性偏頭痛的痛覺感受器反復(fù)激活模型成功。2、PKC可以調(diào)節(jié)機(jī)械痛閾值以及CGRP、c-Fos的表達(dá)變化,提示PKC參與慢性偏頭痛中樞敏化的病理生理過程。
[Abstract]:Background: migraine is a common primary headache with recurrent episodes. Headache is characterized by unilateral, pulsating, moderate to severe and aggravation of daily activity. It is accompanied by nausea, vomiting, photophobia and awe. The incidence of migraine is high, and its recurrent attacks seriously affect the work and quality of life of the patients. It has brought a serious burden to individuals, families and society, which has been listed as one of the four most serious chronic dysfunction diseases of the WHO. Migraine can be divided into episodic migraine (EM) and chronic migraine (chronic migraine, CM) according to the frequency of its attack. The clinical diagnostic criteria for chronic migraine are: a large monthly headache attack. Chronic migraine is a common complication of migraine on 15 days. Chronic migraine is a common complication of migraine. About 2.5% of the migraine migraine into chronic migraine every year is more serious than EM for individuals, family and society. So how to prevent the chronicity of migraine is a major problem in the field of Neurology. In recent years, many studies have found that central sensitization plays an important role in the chronicity of migraine. Therefore, further study of the central sensitization mechanism of migraine and the inhibition of the chronicity of migraine is an important way to seek new targets for migraine, and it is very important to improve the quality of life of migraine patients. Previous studies have found that in a variety of pain models, PKC activity is significantly increased, and the inhibition of PKC activity can significantly reduce pain, suggesting that PKC plays an important role in the process of central sensitization of pain. But whether PKC is involved in the central sensitization mechanism of chronic migraine has not been reported, so this article is aimed at this article. Study whether PKC is involved in the pathophysiological process of chronic migraine through central sensitization. Methods: 1, the experimental group: SD male rats were randomly divided into 7 groups of.A, sham operation group (n=11), PBS2 mu l.B, model group (n=12), 7 days of epidural continuous infusion of IS2 u l.C, model + solvent group (n=8), 7 days of epidural continuous infusion of IS2 micron, lateral ventricle injection. DMSO5 mu l.D, PKC inhibitor low dose group (n=11), IS2 Mu L for 7 days in epidural continuous infusion, CHE4 mu g (5 L).E for lateral ventricle, PKC inhibitor in high dose group (n=10). C agonist high dose group (n=11), 7 days of epidural continuous infusion of IS2 Mu L, lateral ventricle injection of PMA200ng (5 L).2, extradural catheter, two days after the operation, select the wound not infected, the catheter unblocked rats enter the next experiment. Give IS or PBS slow dural infusion, repeat 7 days. Simulation of the reactivation of the dura meninges, the establishment of a slow activation, establish slow, slow establishment of the dura. .3, a rat model of migraine, after the establishment of a chronic migraine rat model, the lateral ventricle gave the PKC inhibitor CHE and PKC agonist PMA. Von Frey test was used to determine the mechanical pain threshold of the rat's face and hind feet. Western blot and immunofluorescence test TNC site PKC. After stimulating the dura, the threshold of mechanical pain in the face and foot of the rat decreased significantly, while the expression of CGRP, c-Fos and PKC protein in the nucleus of the trigeminal nucleus was significantly increased by.2. The pain threshold of the face and foot in the rat could be significantly increased with the use of CHE to inhibit PKC, and the CGRP, c-Fos expression was significantly reduced, while PMA activated PKC decreased the pain threshold, and the pain threshold was reduced significantly. Significant reduction of pain threshold was made with PMA activation. Significant pain threshold was reduced significantly. Increase the expression of CGRP and c-Fos. Conclusion: 1,.2 is successfully used to stimulate the model of chronic migraine in the dural mimic rats by repeated stimulation of the inflammatory soup. PKC can regulate the threshold of mechanical pain and the changes in the expression of CGRP and c-Fos, suggesting that PKC is involved in the pathophysiological process of central sensitization of chronic migraine.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R747.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前5條

1 裴培;劉璐;趙洛鵬;崔瑩雪;王麟鵬;;偏頭痛:中樞敏化與皮膚異常性疼痛[J];中國疼痛醫(yī)學(xué)雜志;2016年02期

2 譚亮;樊光輝;;偏頭痛發(fā)病機(jī)制的研究進(jìn)展[J];中國臨床神經(jīng)外科雜志;2012年09期

3 鄭穎;張偉;朱昱;艾青龍;;慢性偏頭痛的研究進(jìn)展[J];國際神經(jīng)病學(xué)神經(jīng)外科學(xué)雜志;2012年04期

4 王遠(yuǎn)勝,胡興國;蛋白激酶C與疼痛的中樞敏感化[J];國外醫(yī)學(xué).麻醉學(xué)與復(fù)蘇分冊;2002年02期

5 倪同尚,武勝昔,李云慶;蛋白激酶C的分子生物學(xué)特征及研究進(jìn)展[J];解剖科學(xué)進(jìn)展;2001年04期

，

本文編號：1997994