本文關(guān)鍵詞：海馬AMPARs參與腸易激綜合征大鼠中樞敏化　出處：《福建醫(yī)科大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 慢性功能性內(nèi)臟痛 長時(shí)程增強(qiáng) AMPARs 海馬 腸易激綜合征

【摘要】：目的探究海馬α-氨基-3-羥基-5-甲基4-異嗯唑丙酸受體(a-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptor,AMPARs)在腸易激綜合征(Irritable bowel syndrome,IBS)慢性功能性內(nèi)臟痛大鼠中樞敏化的作用及機(jī)制,以期揭示IBS慢性功能性內(nèi)臟痛發(fā)病機(jī)制,為IBS慢性功能性內(nèi)臟痛臨床防治及藥物研發(fā)提供新思路。方法新生SD大鼠出生后第3~21天,每天固定時(shí)間給予3小時(shí)母嬰分離心理應(yīng)激,構(gòu)建IBS慢性內(nèi)臟痛模型,對照組大鼠除不行母嬰分離外,其他處理方式均與模型組一致。大鼠成年后(8周),通過檢測40和60 mm Hg結(jié)直腸擴(kuò)張刺激下腹外斜肌放電反應(yīng)的方法評估模型成功與否,選痛覺敏化者進(jìn)行實(shí)驗(yàn)。經(jīng)立體定位置管,海馬雙側(cè)微量注射不同劑量的AMPARs抑制劑CNQX(10、20、40 nmol,每側(cè)2μl),觀察比較給藥前后不同壓力下腹外斜肌放電反應(yīng)的差異及藥效持續(xù)時(shí)間。通過Western blot方法檢測比較正常和IBS大鼠海馬AMPARs亞型(Glu R1,Glu R2)的表達(dá)水平;應(yīng)用離體腦片場電位記錄方法觀察IBS大鼠海馬CA1區(qū)長時(shí)程增強(qiáng)(long-term potential,LTP)是否易化,并在高頻刺激60min后,取海馬腦片通過Western blot檢測其Glu R1、Glu R2的表達(dá)情況。結(jié)果①IBS慢性功能性內(nèi)臟痛大鼠內(nèi)臟痛敏反應(yīng)較正常大鼠顯著增高。②海馬雙側(cè)微量注射AMPARs抑制劑CNQX可劑量依賴性抑制大鼠內(nèi)臟痛敏反應(yīng),抑制作用在給藥后30min最強(qiáng),可持續(xù)約90min。③與對照組大鼠相比,IBS慢性功能性內(nèi)臟痛大鼠AMPARs的亞型Glu R2表達(dá)量顯著增高,然而Glu R1的表達(dá)水平卻無明顯差異。④IBS慢性功能性內(nèi)臟痛大鼠,高頻刺激誘導(dǎo)的海馬LTP與正常大鼠相比顯著增強(qiáng)。⑤正常和IBS慢性功能性內(nèi)臟痛大鼠離體腦片高頻刺激誘導(dǎo)的長時(shí)程增強(qiáng)可使海馬Glu R2表達(dá)水平增高,而對Glu R1表達(dá)量無明顯影響。結(jié)論新生期母嬰分離應(yīng)激可導(dǎo)致大鼠海馬AMPARs的Glu R2亞型上調(diào)及CA1區(qū)長時(shí)程增強(qiáng)易化,從而導(dǎo)致大鼠成年后內(nèi)臟痛敏。
[Abstract]:Objective to explore the hippocampal alpha amino -3- hydroxy -5- methyl 4- ISO oxazole propionic acid receptor (a-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptor, AMPARs) in irritable bowel syndrome (Irritable bowel, syndrome, IBS) the role and mechanism of central sensitization of chronic functional visceral pain in rats, in order to reveal IBS chronic functional visceral pain pathogenesis, provide a new IBS thought for chronic functional visceral pain clinical prevention and drug development. The first 3~21 days after birth of neonatal SD rats, fixed time every day to give 3 hours of maternal separation of psychological stress, construction of IBS chronic visceral pain model, the rats in control group except no maternal separation, other treatments were consistent with the model group rats. Adult (8 weeks), abdominal distension method of external oblique discharge reaction by detecting 40 and 60 mm Hg colorectal evaluation model of success, hyperalgesia were selected by three-dimensional experiments. Location of catheter, trace bilateral hippocampal injection of different doses of AMPARs inhibitor CNQX (10,20,40 nmol, each side of 2 L), were observed and compared before and after administration of different pressure abdominal external oblique discharge reaction and duration of action. By detecting the Western blot method to compare normal and AMPARs in hippocampus of rats with IBS subtype (Glu R1, Glu the expression level of R2); application of in vitro brain field potential recording method to observe the IBS in rat hippocampal CA1 long-term potentiation (long-term, potential, LTP) is easy, and the high frequency stimulation after 60min from hippocampal slices by Western blot to detect the expression of Glu Glu R1, R2. Results IBS chronic function visceral pain in rats with visceral hypersensitivity reaction than normal rats increased markedly. The bilateral hippocampal microinjection of AMPARs inhibitor CNQX could dose dependently inhibit the rat visceral hypersensitivity reaction inhibition after administration of 30min is the highest, lasts about 90min. Compared with control rats, IBS chronic functional visceral pain in rats of AMPARs subtype Glu R2 expression was significantly increased, but no significant difference between the expression level of Glu R1. The IBS of chronic functional visceral pain rats induced by high frequency stimulation in hippocampal LTP increased compared with normal rats. Brain slices induced by high frequency stimulation in the normal and IBS chronic functional visceral pain rats potentiation of hippocampal Glu R2 expression level can be increased, and the Glu R1 expression had no obvious effect. Conclusion the neonatal maternal separation stress can induce AMPARs rat hippocampal Glu subtype R2 and upregulation of CA1 region process to strengthen, resulting in adult rats with visceral hypersensitivity.

【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R574.4

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相關(guān)期刊論文 前1條

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本文編號：1393654