L型前列腺素合酶在大鼠病理性痛模型中的表达调控研究

发布时间：2018-07-03 00:25

本文选题：L型前列腺素合酶 + 背根神经元　；参考：《中国科学院研究生院（上海生命科学研究院）》2006年硕士论文

【摘要】：已有的研究表明前列腺素及合酶在炎症发生发展和痛觉的调制中起非常重要的作用,一些前列腺素合酶的抑制剂可以作为解热镇痛抗炎药。目前阿斯匹林等非甾类抗炎剂主要的作用靶分子为环氧化酶,对所有组织因炎症而导致的疼痛均有效,但长期使用,可引起许多副作用。因此研究前列腺素及合酶参与疼痛调制的机理,将有利于发展新的高效低副作用的非甾类抗炎剂。L型前列腺素合酶(L-PGDS)催化普通前列腺素类化合物前体PGH_2的异构化反应,是一种脑源性和不依赖谷胱甘肽的酶,生成与痛觉有关的分子PGD_2。本论文的主要目的是研究L-PGDS在初级感觉神经节中的表达和在慢性疼痛中的调控改变。用免疫组织化学方法研究表明,在背根神经节(DRG)的小神经元中可以检测到有L-PGDS的表达,且位于降钙素基因相关肽(CGRP)阳性的小神经元中,在亚细胞结构上L-PGDS与含CGRP的囊泡样结构共存,这类含有L-PGDS的神经元可以投射到脊髓背角浅层。在大鼠外周神经损伤和福氏佐剂所致的慢性炎症模型中,用微阵列检测方法发现其表达均有增加,用RT-PCR进一步证实了L-PGDS的mRNA水平表达的增加。初步用PGD_2鞘内注射可以诱发大鼠的机械性痛敏发生,鞘内注射PGD_2受体的选择性抑制剂可以降低慢性炎症模型所致的痛觉过敏。本研究结果表明L-PGDS可能在慢性痛的发生过程中起作用,为寻找镇痛靶点提供机制。
[Abstract]:Previous studies have shown that prostaglandins and synthase play a very important role in the development of inflammation and modulation of pain. Some inhibitors of prostaglandin synthase can be used as antipyretic analgesic and anti-inflammatory drugs. At present, the main target molecule of non-steroidal anti-inflammatory agents, such as aspirin, is cyclooxygenase, which is effective for pain caused by inflammation in all tissues, but long-term use can cause many side effects. Therefore, to study the mechanism of prostaglandins and synthase involved in pain modulation will be helpful to develop a new non-steroidal anti-inflammatory agent. L-type prostaglandin synthase (L-PGDS) catalyzes the isomerization of prostaglandins precursor PGH2. It is a brain-derived and glutathione-independent enzyme that produces a pain-related molecule, PGD _ 2. The aim of this study was to investigate the expression of L-PGDS in primary sensory ganglion and its regulatory changes in chronic pain. Immunohistochemical study showed that L-PGDS expression could be detected in small neurons of dorsal root ganglion (DRG), and it was located in calcitonin gene-related peptide (CGRP) positive small neurons. In the subcellular structure, L-PGDS coexisted with CGRP-containing vesicular structure, and the neurons containing L-PGDS could project to the superficial layer of the dorsal horn of spinal cord. In the rat model of peripheral nerve injury and chronic inflammation induced by Freund's adjuvant, the expression of L-PGDS mRNA was detected by microarray method, and the expression of L-PGDS mRNA was further confirmed by RT-PCR. Intrathecal injection of PGD2 could induce mechanical hyperalgesia in rats, and the selective inhibitor of PGD2 receptor could reduce the hyperalgesia induced by chronic inflammation. These results suggest that L-PGDS may play a role in the pathogenesis of chronic pain and provide a mechanism for finding analgesic targets.
【学位授予单位】：中国科学院研究生院（上海生命科学研究院）
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R363

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