本文關(guān)鍵詞：ERK在偏頭痛動(dòng)物模型中的激活及與肥大細(xì)胞脫顆粒間的關(guān)系　出處：《山西醫(yī)科大學(xué)》2011年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 偏頭痛 細(xì)胞外信號調(diào)節(jié)激酶 肥大細(xì)胞 硬腦膜 三叉神經(jīng)核尾部 硝酸甘油 大鼠

【摘要】：目的:通過觀察硝酸甘油(GTN)誘導(dǎo)的大鼠偏頭痛模型中硬腦膜和三叉神經(jīng)核尾部磷酸化細(xì)胞外信號調(diào)節(jié)激酶(p-ERK)的表達(dá)情況,及p-ERK的表達(dá)與肥大細(xì)胞脫顆粒間的關(guān)系,揭示p-ERK在偏頭痛發(fā)病過程中的病理生理作用,為偏頭痛的治療提供新的實(shí)驗(yàn)依據(jù)。 方法:將72只雄性SD大鼠隨機(jī)分為偏頭痛模型組(n=54)和空白對照組(n=18),模型組采用皮下注射GTN(10mg/kg)法建立大鼠偏頭痛模型,再將模型組大鼠隨機(jī)分為三個(gè)亞組:Compound48/80組(腹腔注射Compound48/80,2mg/kg);SCG+Compound48/80組(腹腔先注射SCG, 10mg/kg后再注射Compound48/80, 2mg/kg)和實(shí)驗(yàn)對照組(腹腔注射同等劑量的生理鹽水),空白對照組大鼠皮下注射等量生理鹽水。應(yīng)用免疫組織化學(xué)染色法觀察模型組各亞組大鼠分別在腹腔注射Compound48/80、SCG+Compound48/80、生理鹽水的15min、60min、120min后硬腦膜、三叉神經(jīng)核尾部磷酸化ERK(p-ERK)的表達(dá)情況;空白對照組給予等量生理鹽水與GTN組對照,也分別在15min、60min、120min后取硬腦膜、三叉神經(jīng)核尾部觀察p-ERK的表達(dá)情況。 結(jié)果:1)行為學(xué)觀察:63只雄性SD大鼠注射GTN,誘發(fā)偏頭痛模型成功57只(成功率為90.4%),造模5～15min左右大鼠出現(xiàn)雙耳發(fā)紅、頻繁撓頭、煩躁亂動(dòng)的現(xiàn)象,約40～60min達(dá)高峰,此現(xiàn)象持續(xù)1～3h,繼之大鼠呈現(xiàn)活動(dòng)減少、倦臥狀態(tài)。而Compound48/80組和SCG+Compound48/80組頻繁撓頭、爬籠次數(shù)增多等煩躁現(xiàn)象約18～30min時(shí)達(dá)高峰。空白對照組僅在15min內(nèi)略有撓頭現(xiàn)象,之后趨于正常,且未出現(xiàn)雙耳發(fā)紅、爬籠次數(shù)增多等現(xiàn)象。2)鏡下觀察:免疫組織化學(xué)染色發(fā)現(xiàn)空白對照組大鼠各時(shí)間點(diǎn)硬腦膜、三叉神經(jīng)核尾部均有少量p-ERK陽性免疫反應(yīng)產(chǎn)物;模型組各亞組各時(shí)間點(diǎn)硬腦膜、三叉神經(jīng)核尾部均有較空白對照組對應(yīng)時(shí)間點(diǎn)染色深而多的p-ERK陽性免疫反應(yīng)產(chǎn)物,以模型組Compound48/80亞組的15min組最為顯著,且這些陽性免疫反應(yīng)產(chǎn)物主要分布于脫顆粒的肥大細(xì)胞附近。3)統(tǒng)計(jì)結(jié)果:ERK在模型組各亞組和空白對照組的各時(shí)間點(diǎn)硬腦膜和三叉神經(jīng)核尾部都發(fā)生了磷酸化,但空白對照組的各時(shí)間點(diǎn)間無顯著差異(P0.05);模型組各亞組各時(shí)間點(diǎn)p-ERK陽性免疫反應(yīng)產(chǎn)物都顯著高于空白對照組對應(yīng)時(shí)間點(diǎn)(P0.05);模型組Compound48/80亞組各時(shí)間點(diǎn)p-ERK的陽性免疫產(chǎn)物顯著高于SCG+ Compound48/80組和實(shí)驗(yàn)對照組對應(yīng)時(shí)間點(diǎn)(P0.05);模型組各亞組15min組分別顯著高于同組的60min組和120min組(P0.05)。 結(jié)論:皮下注射GTN后,大鼠硬腦膜和三叉神經(jīng)核尾部處p-ERK的表達(dá)增加,且與肥大細(xì)胞脫顆粒的數(shù)量呈正相關(guān),但隨時(shí)間的延長磷酸化的ERK會(huì)失活,提示ERK可能參與了偏頭痛早期痛覺信號的傳導(dǎo),肥大細(xì)胞脫顆�？赡苁谴偈筽-ERK表達(dá)增加的原因,支持三叉神經(jīng)血管炎癥學(xué)說。
[Abstract]:Objective: to observe the expression of extracellular signal regulated kinase (ERK) in dural and trigeminal nucleus of rats with migraine induced by GTNN. The relationship between the expression of p-ERK and mast cell degranulation reveals the pathophysiological role of p-ERK in the pathogenesis of migraine and provides a new experimental basis for the treatment of migraine. Methods: 72 male Sprague-Dawley rats were randomly divided into migraine model group (n = 54) and blank control group (n = 18). In the model group, the migraine model was established by subcutaneous injection of GTNN 10 mg / kg. Then the model group rats were randomly divided into three subgroups:: component 48 / 80 (intraperitoneal injection of Compound48 / 802 mg / kg); SCG Compound48/80 group (SCG was injected intraperitoneally, 10 mg / kg then Compound48/80). 2 mg / kg) and experimental control group (intraperitoneal injection of the same dose of normal saline). The rats in the blank control group were subcutaneously injected with the same amount of normal saline. The rats of each subgroup of the model group were respectively injected with Compound48/80 in the abdominal cavity by immunohistochemical staining. SCG component 48 / 80, normal saline 15 mins, 60 mins, 120 minutes later, dura mater. The expression of phosphorylated ERK p-ERK in the tail of trigeminal nucleus; The same amount of normal saline was given to the blank control group and the control group, and the expression of p-ERK was observed at the end of trigeminal nucleus, and the dura mater was taken 120 minutes after 15 min or 60 min. Results the behavior of 63 male Sprague-Dawley rats was observed by behavior observation. 57 rats were successfully induced migraine (success rate was 90.4%) by injecting GTNN into male Sprague-Dawley rats. The rats showed redness of ears, frequent scratching of their heads and agitation for about 15 minutes, and reached the peak for about 4060 minutes. This phenomenon lasted for 1 minute for 3 hours, followed by a decrease in the activity of the rats. While Compound48/80 group and SCG Compound48/80 group frequently scratched their heads. The number of cage climbing increased and so on, which reached the peak at 1830 minutes. The blank control group only slightly scratched its head within 15 minutes, then tended to normal, and did not appear auricular redness. Observation under microscope: immunohistochemical staining showed that there were a small amount of p-ERK positive immunoreactive products in the dura mater and tail of trigeminal nucleus of rats in the blank control group at every time point. Compared with the blank control group, there were more p-ERK positive immunoreactive products in the dural and the tail of trigeminal nucleus in each subgroup of model group than in the blank control group. The Compound48/80 subgroup of model group was the most significant in 15min group. These immunoreactive products were mainly distributed near degranulated mast cells. 3). The results showed that the phosphorylation of the dura mater and the tail of trigeminal nucleus occurred at all time points in the model group and the blank control group. However, there was no significant difference between different time points in the blank control group (P 0.05). The p-ERK positive immunoreactive products in each subgroup of the model group were significantly higher than those in the blank control group at each time point (P0.05). The positive immunoreactive products of p-ERK in Compound48/80 subgroup of model group were significantly higher than those in SCG Compound48/80 group and experimental control group at each time point. P0.05; The 15min group of each subgroup in the model group was significantly higher than that in the 60min group and 120min group in the same group. Conclusion: after subcutaneous injection of GTN, the expression of p-ERK in dural and trigeminal nucleus of rats was increased, and it was positively correlated with the number of mast cell degranulation. However, phosphorylated ERK will be inactivated over time, suggesting that ERK may be involved in the early migraine pain signal transduction, mast cell degranulation may be the cause of the increase of p-ERK expression. Supports the theory of trigeminal neurovascular inflammation.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R747.2;R-332

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