本文關(guān)鍵詞： 環(huán)氧合酶 前列腺素 吲哚美鋅 尼美舒利 β-內(nèi)啡肽 μ阿片受體　出處：《福建師范大學(xué)》2011年碩士論文　論文類型：學(xué)位論文

【摘要】：環(huán)氧合酶是合成前列腺素過程中的關(guān)鍵酶。它主要有兩種形式：環(huán)氧合酶-1是組成型酶,在各組織中均有表達(dá)；環(huán)氧合酶-2為誘導(dǎo)型酶,只在組織損傷或細(xì)胞因子的刺激下表達(dá)上調(diào),與炎癥痛敏有密切關(guān)系。 內(nèi)源性阿片肽是在哺乳動物體內(nèi)合成的具有阿片樣活性的肽類物質(zhì)。它通過與阿片受體結(jié)合發(fā)揮鎮(zhèn)痛或抗傷害性作用。炎癥組織中的內(nèi)源性阿片肽主要由免疫細(xì)胞產(chǎn)生并釋放。 本實(shí)驗(yàn)應(yīng)用行為學(xué),免疫組織化學(xué),蛋白質(zhì)印跡和酶聯(lián)免疫吸附等實(shí)驗(yàn)方法研究環(huán)氧合酶在角叉菜膠致炎大鼠外周炎癥組織內(nèi)源性阿片系統(tǒng)表達(dá)中的作用。實(shí)驗(yàn)結(jié)果顯示,大鼠足跖皮下注射角叉菜膠致炎后1小時,注射環(huán)氧合酶非選擇性抑制劑吲哚美鋅能夠劑量依賴性地使大鼠在第2天和第3天產(chǎn)生痛覺低敏現(xiàn)象,并且炎癥組織內(nèi)β-內(nèi)啡肽表達(dá)顯著升高；注射角叉菜膠致炎后1小時,注射環(huán)氧合酶-2選擇性抑制劑尼美舒利在第2天和第3天及第4天均產(chǎn)生痛覺低敏現(xiàn)象,并且引起炎癥組織內(nèi)含β-內(nèi)啡肽的陽性細(xì)胞數(shù)量顯著升高；同時,同側(cè)背根神經(jīng)節(jié)內(nèi)μ阿片受體的表達(dá)量也明顯上調(diào)。 本研究表明,通過抑制外周炎癥組織中的環(huán)氧合酶以阻斷前列腺素的合成能夠增強(qiáng)炎癥組織內(nèi)源性阿片肽的表達(dá)和背根神經(jīng)節(jié)內(nèi)阿片受體上調(diào),從而發(fā)揮了一定的鎮(zhèn)痛作用。這為闡明炎癥疼痛產(chǎn)生的機(jī)制、開發(fā)外周鎮(zhèn)痛藥提供了理論參考。
[Abstract]:Cyclooxygenase is a key enzyme in the synthesis of prostaglandins. It has two main forms: cyclooxygenase-1 is a constitutive enzyme and expressed in all tissues; Cyclooxygenase-2 is an inducible enzyme, which is only up-regulated by tissue injury or cytokine stimulation, and is closely related to inflammatory pain sensitivity. Endogenous opioid peptides are opioid-like peptides synthesized in mammals. They perform analgesic or anti-nociceptive effects by binding to opioid receptors. Endogenous opioid peptides in inflammatory tissues are mainly immunized. Cells are produced and released. Behavior and immunohistochemistry were used in this experiment. Western blot and enzyme-linked immunosorbent assay (Elisa) were used to study the role of cyclooxygenase in the expression of endogenous opioid system in the peripheral inflammatory tissues of carrageenin-induced inflammation rats. One hour after hypodermic injection of carrageenin into the plantar of rats, injection of indomethacin, a non-selective inhibitor of cyclooxygenase, could induce pain hypersensitivity in rats on day 2 and day 3 in a dose-dependent manner. The expression of 尾 -endorphin in inflammatory tissues was significantly increased. One hour after the injection of carrageenin, nimesulide, a selective inhibitor of cyclooxygenase-2, produced pain hypersensitivity on the 2nd, 3rd and 4th day. The number of 尾 -endorphin positive cells in inflammatory tissue was significantly increased. At the same time, the expression of 渭 opioid receptor in ipsilateral dorsal root ganglion was up-regulated. This study suggests that blocking the synthesis of prostaglandins by inhibiting cyclooxygenase in peripheral inflammatory tissues can enhance the expression of endogenous opioid peptides and up-regulate opioid receptors in dorsal root ganglion. It provides a theoretical reference for elucidating the mechanism of inflammatory pain and developing peripheral analgesics.
【學(xué)位授予單位】：福建師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R363

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