發(fā)布時間：2018-03-10 23:28

  本文選題：前列腺酸性磷酸酶　切入點：慢性痛　出處：《第四軍醫(yī)大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：慢性疼痛作為一種嚴(yán)重危害人類身心健康的疾病，已經(jīng)引起全世界的高度重視，但由于其病理機(jī)制十分復(fù)雜，尚缺乏有效的治療手段，特別是能夠治療慢性疼痛的特效藥物不多。動物行為學(xué)研究表明，前列腺酸性磷酸酶（prostatic acid phosphatase, PAP）在神經(jīng)病理性痛及炎性痛模型動物中具有良好的鎮(zhèn)痛效果，但是，慢性痛狀態(tài)下PAP在脊髓背角和背根神經(jīng)節(jié)的表達(dá)變化模式尚未見系統(tǒng)報道。 為進(jìn)一步研究PAP這種潛在的新型鎮(zhèn)痛劑參與鎮(zhèn)痛的機(jī)理，本研究運用免疫組織化學(xué)技術(shù)，觀察了PAP在初級傳入的定位分布，并探討了PAP參與鎮(zhèn)痛的神經(jīng)學(xué)機(jī)制。本實驗的主要結(jié)果如下： 1. PAP在大鼠脊髓背角和背根神經(jīng)節(jié)的分布 免疫組織化學(xué)染色結(jié)果顯示，，PAP陽性反應(yīng)產(chǎn)物主要定位于在背根神經(jīng)節(jié)（dorsal root ganglion, DRG）中的中、小型神經(jīng)元細(xì)胞膜和核周區(qū)域，以及脊髓背角（spinal dorsal horn, SDH）II層內(nèi)的初級傳入終末。 2. PAP陽性神經(jīng)元及其初級傳入終末的化學(xué)神經(jīng)解剖學(xué)特性 免疫熒光三重標(biāo)記染色結(jié)果顯示，PAP與非肽能神經(jīng)元標(biāo)記物異凝集素B4（isolectin B4, IB4）廣泛共存于陽性神經(jīng)元及其終末；少量PAP陽性神經(jīng)元及其終末同時表達(dá)肽能神經(jīng)元標(biāo)記物P物質(zhì)（substance P, SP）或降鈣素基因相關(guān)肽（calcitonin gene-related peptide, CGRP）；在脊髓背角Ⅱ?qū)由畈浚锌梢娚倭縋AP陽性初級傳入終末與中間神經(jīng)元標(biāo)記物蛋白激酶Cγ亞單位（protein kinase C γ subunit, PKCγ）陽性神經(jīng)元的分布區(qū)域重疊。免疫熒光雙重標(biāo)記染色結(jié)果顯示，腺苷A1受體（adenosine A1receptor, A1R）主要表達(dá)于DRG大型神經(jīng)元，DRG中未見PAP與A1R雙標(biāo)神經(jīng)元。 3. PAP在慢性痛大鼠脊髓背角和背根神經(jīng)節(jié)的表達(dá)變化 免疫組織化學(xué)染色結(jié)果顯示，PAP在神經(jīng)損傷所致的神經(jīng)病理性痛和骨癌痛模型大鼠手術(shù)側(cè)SDH和DRG的表達(dá)呈不同程度降低，且PAP表達(dá)減少量與神經(jīng)損傷程度相關(guān)；但PAP在炎性痛大鼠模型兩側(cè)SDH和DRG表達(dá)未見明顯下降。 本課題研究表明：PAP定位于DRG的中、小型神經(jīng)元和脊髓背角Ⅱ?qū)由畈康慕K末；PAP主要表達(dá)于非肽能傷害性神經(jīng)元及其終末；神經(jīng)病理性痛和骨癌痛可使PAP減少，而炎性痛刺激則對PAP無影響；DRG中未見PAP與A1R雙標(biāo)神經(jīng)元。上述結(jié)果提示PAP通過非肽能的傷害性初級傳入影響痛信息的傳遞，周圍神經(jīng)損傷可能影響內(nèi)源性PAP在外周的合成及其沿初級傳入向脊髓的運輸。
[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 緯 subunit (PKC 緯) 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

本文編號：1595550