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感觉神经元特异性受体激动剂BAM8-22和肾上腺髓质素在吗啡耐受中的作用及机制

作　者: 陈佩文
导　师: 洪炎国
学　校: 福建师范大学
专　业: 动物学
关键词: 牛肾上腺髓质8-22 牛肾上腺髓质22 肾上腺髓质素吗啡耐受降钙素基因相关肽脊髓背根神经节
分类号: R96
类　型: 硕士论文
年　份: 2009年
下　载: 11次
引　用: 3次
阅　读: 论文下载

内容摘要

感觉神经元特异性受体(sensory neuron-specific receptor,SNSR)mRNA只特异性地分布于背根神经节(dorsal root ganglia,DRG)和三叉神经节(trigeminal ganglia,TG)的小型感觉神经元内,应用其激动剂牛肾上腺髓质素8-22(bovine adrenalmedulla 8-22,BAM8-22)可以部分抑制吗啡耐受的形成,但其机制还不清楚。肾上腺髓质素(adrenomedullin,AM)是降钙素基因相关肽(calcitonin gene related peptide,CGRP)超家族中的一员,与CGRP具有相似的结构和功能。已知AM参与了炎症痛的形成和维持。本研究应用行为学,组织学和生物化学等实验方法研究了:(1)慢性吗啡作用对牛肾上腺髓质素22(bovine adrenal medulla 22,BAM22)和AM表达的影响及机制;(2)SNSR和AM受体对吗啡耐受的影响及机制。结果显示:慢性给予吗啡会导致脊髓背角及DRG内BAM22的表达下调和AM的表达上调。蛋白激酶C(proteinkinase C,PKC)介导了慢性吗啡作用导致的AM表达上调,而蛋白激酶A(proteinkinase A,PKA)不参与此过程;间隔鞘内注射BAM8-22可以完全抑制吗啡耐受的形成,其机制与调节BAM22,神经元型一氧化氮合酶(neuronal nitric oxide synthesis,nNOS)和CGRP等神经递质或调质的表达有关;鞘内注射AM受体拮抗剂肾上腺髓质素22-52(adrenomedullin 22-52,AM22-52)可以剂量依赖性的抑制吗啡耐受的形成,并且可以部分翻转吗啡耐受。AM22-52抑制和翻转吗啡耐受的作用是通过调节AM,CGRP,nNOS和BAM22等的表达来实现的。这些结果提示了镇痛性介质的表达减少或致痛性介质的增加是吗啡耐受形成的原因之一;本研究表明SNSR激活能抑制吗啡耐受,AM参与了吗啡耐受的形成和维持。

全文目录

中文摘要  2-3
Abstract  3-4
中文文摘  4-7
Table of contents  7-10
Literature review  10-20
  Ⅰ.The transmission of nociceptive information  10-12
  Ⅱ.The mechanism of morphine antinociception  12
  Ⅲ.Cellular mechanisms of morphine tolerance  12-20
    1.MOR and morphine tolerance  12-13
    2.Role of nociceptive mediators in morphine tolerance  13-20
Chapter 1 The expression of bovine adrenal medulla 22-like immunoreactivity in the spinal cord and DRG of rats following treatment with chronic morphine  20-26
  1.1 Materials and methods  20-23
    1.1.1 Animals  20
    1.1.2 Drugs  20-21
    1.1.3 Catheterization implantation and injections  21
    1.1.4 Immunocytochemistry and Immunofluorescence staining  21-22
    1.1.5 Data analyses  22-23
  1.2 Results Effect of chronic morphine on the expression of BAM22-IR in the spinal cord and DRG  23-24
  1.3 Discussion  24-26
Chapter 2 Effect of BAM8-22 on the development of morphine tolerance  26-40
  2.1 Materials and methods  26-29
    2.1.1 Animals  26
    2.1.2 Drugs  26
    2.1.3 Catheterization implantation and injections  26
    2.1.4 Behavioral assessment  26-27
    2.1.5 Immunocytochemistry and Immunofluorescence staining  27
      2.1.5.1 ABC staining  27
      2.1.5.2 Immunofluorescence staining  27
    2.1.6 DRG explant culture  27
    2.1.7 Enzyme-linked immunoassay(ELISA) of CGRP  27-28
    2.1.8 Data analyses  28-29
  2.2 Results  29-36
    2.2.1 Effect of daily or intermittent i.t.BAM8-22 on development of morphine tolerance  29-31
    2.2.2 Effect of intermittent i.t.BAM8-22 on the decrease of BAM22 expression following chronic application of morphine  31-32
    2.2.3 Effect of intermittent administration of BAM8-22 on morphine-induced increase in nNOS expression  32-34
    2.2.4 Effect of intermittent i.t.BAM8-22 on the morphine-induced up-regulation of CGRP  34-36
  2.3 Discussion  36-40
Chapter 3 Effect of chronic administration of morphine on the expression of adrenomedullin in the spinal cord and ganglia  40-46
  3.1 Materials and methods  40-41
    3.1.1 Animals  40
    3.1.2 Drugs  40
    3.1.3 Catheterization implantation and injections  40
    3.1.4 Immunocytochemistry  40-41
    3.1.5 DRG explant culture  41
    3.1.6 Enzyme-linked immunoassay(ELISA) of AM  41
    3.1.7 Data analyses  41
  3.2 Results  41-44
    3.2.1 Effect of i.t.administration of morphine on the expression of AM-IR in the DRG and spinal cord  41-42
    3.2.2 The mechanisms of the increase expression of AM following chronic treatment with morphine  42-44
  3.3 Discussion  44-46
Chapter 4 Effect of AM22-52 on morphine tolerance  46-62
  4.1 Materials and methods  46
    4.1.1 Animals  46
    4.1.2 Drugs  46
    4.1.3 Catheterization implantation and injections  46
    4.1.4 Behavioral assessment  46
    4.1.5 Immunocytochemistry and Immunofluorescence staining  46
    4.1.6 Data analyses  46
  4.2 Results  46-58
    4.2.1 Effects of AM22-52 on the development and maintenance of morphine tolerance  47-50
    4.2.2 Effects of AM22-52 on acute morphine antinociception  50
    4.2.3 Effect of AM22-52 on morphine-induced changes in AM-IR in the spinal cord and DRG  50-52
    4.2.4 Effect of AM22-52 on morphine-induced increase in CGRP expression in the spinal cord and DRG  52-54
    4.2.5 Effect of i.t.AM22-52 on morphine-induced increase of nNOS expression  54-56
    4.2.6 Effect of i.t.AM22-52 on morphine-induced down-regulation of BAM22 expression  56-58
  4.3 Discussion  58-62
Chapter 5 Conclusions  62-64
Abbreviations  64-66
Reference List  66-80
攻读学位期间承担的科研任务与主要成果  80-82
Acknowledgements  82-84
Curriculum vitae  84

感觉神经元特异性受体激动剂BAM8-22和肾上腺髓质素在吗啡耐受中的作用及机制

内容摘要

全文目录

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