前列腺酸性磷酸酶在慢性痛大鼠脊髓背角和背根神经节表达变化的形态学研究

发布时间：2018-03-10 23:28

  本文选题：前列腺酸性磷酸酶　切入点：慢性痛　出处：《第四军医大学》2012年硕士论文　论文类型：学位论文

【摘要】：慢性疼痛作为一种严重危害人类身心健康的疾病，已经引起全世界的高度重视，但由于其病理机制十分复杂，尚缺乏有效的治疗手段，特别是能够治疗慢性疼痛的特效药物不多。动物行为学研究表明，前列腺酸性磷酸酶（prostatic acid phosphatase, PAP）在神经病理性痛及炎性痛模型动物中具有良好的镇痛效果，但是，慢性痛状态下PAP在脊髓背角和背根神经节的表达变化模式尚未见系统报道。 为进一步研究PAP这种潜在的新型镇痛剂参与镇痛的机理，本研究运用免疫组织化学技术，观察了PAP在初级传入的定位分布，并探讨了PAP参与镇痛的神经学机制。本实验的主要结果如下： 1. PAP在大鼠脊髓背角和背根神经节的分布 免疫组织化学染色结果显示，，PAP阳性反应产物主要定位于在背根神经节（dorsal root ganglion, DRG）中的中、小型神经元细胞膜和核周区域，以及脊髓背角（spinal dorsal horn, SDH）II层内的初级传入终末。 2. PAP阳性神经元及其初级传入终末的化学神经解剖学特性 免疫荧光三重标记染色结果显示，PAP与非肽能神经元标记物异凝集素B4（isolectin B4, IB4）广泛共存于阳性神经元及其终末；少量PAP阳性神经元及其终末同时表达肽能神经元标记物P物质（substance P, SP）或降钙素基因相关肽（calcitonin gene-related peptide, CGRP）；在脊髓背角Ⅱ层深部，尚可见少量PAP阳性初级传入终末与中间神经元标记物蛋白激酶Cγ亚单位（protein kinase C γ subunit, PKCγ）阳性神经元的分布区域重叠。免疫荧光双重标记染色结果显示，腺苷A1受体（adenosine A1receptor, A1R）主要表达于DRG大型神经元，DRG中未见PAP与A1R双标神经元。 3. PAP在慢性痛大鼠脊髓背角和背根神经节的表达变化 免疫组织化学染色结果显示，PAP在神经损伤所致的神经病理性痛和骨癌痛模型大鼠手术侧SDH和DRG的表达呈不同程度降低，且PAP表达减少量与神经损伤程度相关；但PAP在炎性痛大鼠模型两侧SDH和DRG表达未见明显下降。 本课题研究表明：PAP定位于DRG的中、小型神经元和脊髓背角Ⅱ层深部的终末；PAP主要表达于非肽能伤害性神经元及其终末；神经病理性痛和骨癌痛可使PAP减少，而炎性痛刺激则对PAP无影响；DRG中未见PAP与A1R双标神经元。上述结果提示PAP通过非肽能的伤害性初级传入影响痛信息的传递，周围神经损伤可能影响内源性PAP在外周的合成及其沿初级传入向脊髓的运输。
[Abstract]:Chronic pain, as a disease that seriously endangers the physical and mental health of human beings, has attracted great attention all over the world. However, due to the complexity of its pathological mechanism, there is still a lack of effective treatment. In particular, there are few special drugs that can treat chronic pain. Animal behavior studies have shown that prostatic acid phosphatase (PAPs) has good analgesic effect in neuropathic pain and inflammatory pain model animals, but, The expression pattern of PAP in spinal dorsal horn and dorsal root ganglion under chronic pain has not been systematically reported. In order to further study the mechanism of PAP, a potential new analgesics, the localization distribution of PAP in primary afferent was observed by immunohistochemical technique. The main results of this experiment are as follows:. 1. Distribution of PAP in dorsal horn and dorsal root ganglion of rat spinal cord. The results of immunohistochemical staining showed that the PAP-positive products were mainly located at the primary afferent terminals in the membrane and perinuclear regions of small neurons in dorsal root ganglion (DRGs) and spinal dorsal horn, SDH)II layer in the dorsal horn of spinal cord. 2. Chemical neuroanatomical characteristics of PAP positive neurons and their primary afferent terminals. The results of immunofluorescence triple labeling showed that PAP and isagglutinin B4isolectin B4 (IB4) were widely present in the positive neurons and their terminals. A few PAP positive neurons and their terminals simultaneously expressed substance P (substance P), or calcitonin gene-related peptide, or calcitonin gene related peptide (calcitonin) in the dorsal horn of spinal cord. A few PAP positive primary afferent terminals were found to overlap with protein kinase C 纬 subunit (PKC 纬) positive neurons. Adenosine A 1 receptor (A 1R) was mainly expressed in large DRG neurons. There were no PAP and A1R double labeled neurons. 3. Expression of PAP in spinal dorsal horn and dorsal root ganglion of chronic pain rats. The results of immunohistochemical staining showed that the expression of SDH and DRG in the surgical side of neuropathic pain induced by nerve injury and bone cancer pain model rats were decreased in varying degrees, and the decrease of PAP expression was related to the degree of nerve injury. However, the expression of PAP in both sides of inflammatory pain rat model SDH and DRG did not decrease significantly. Our study showed that DRG was localized in the small neurons and the terminals in the deep layer 鈪

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