阻断前列腺素合成对外周炎症组织内源性阿片肽表达的影响

发布时间：2018-02-01 22:07

本文关键词： 环氧合酶前列腺素吲哚美锌尼美舒利 β-内啡肽 μ阿片受体　出处：《福建师范大学》2011年硕士论文　论文类型：学位论文

【摘要】：环氧合酶是合成前列腺素过程中的关键酶。它主要有两种形式：环氧合酶-1是组成型酶,在各组织中均有表达；环氧合酶-2为诱导型酶,只在组织损伤或细胞因子的刺激下表达上调,与炎症痛敏有密切关系。内源性阿片肽是在哺乳动物体内合成的具有阿片样活性的肽类物质。它通过与阿片受体结合发挥镇痛或抗伤害性作用。炎症组织中的内源性阿片肽主要由免疫细胞产生并释放。本实验应用行为学,免疫组织化学,蛋白质印迹和酶联免疫吸附等实验方法研究环氧合酶在角叉菜胶致炎大鼠外周炎症组织内源性阿片系统表达中的作用。实验结果显示,大鼠足跖皮下注射角叉菜胶致炎后1小时,注射环氧合酶非选择性抑制剂吲哚美锌能够剂量依赖性地使大鼠在第2天和第3天产生痛觉低敏现象,并且炎症组织内β-内啡肽表达显著升高；注射角叉菜胶致炎后1小时,注射环氧合酶-2选择性抑制剂尼美舒利在第2天和第3天及第4天均产生痛觉低敏现象,并且引起炎症组织内含β-内啡肽的阳性细胞数量显著升高；同时,同侧背根神经节内μ阿片受体的表达量也明显上调。本研究表明,通过抑制外周炎症组织中的环氧合酶以阻断前列腺素的合成能够增强炎症组织内源性阿片肽的表达和背根神经节内阿片受体上调,从而发挥了一定的镇痛作用。这为阐明炎症疼痛产生的机制、开发外周镇痛药提供了理论参考。
[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.
【学位授予单位】：福建师范大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R363

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