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Title: | 巨噬細胞在發炎型神經病變之角色:
於腓腸神經切片之研究 Macrophages in inflammatory neuropathies: a sural nerve biopsy study |
Authors: | Naomi Chu-Chiao Yang 楊筑喬 |
Advisor: | 謝松蒼(Sung-Tsang Hsieh) |
Keyword: | 發炎型神經病變,軸索退化,巨噬細胞,Iba1,AQP4,ApoE, inflammatory neuropathy,axonal degeneration,macrophage,Iba1,AQP4,ApoE, |
Publication Year : | 2009 |
Degree: | 碩士 |
Abstract: | 周邊神經病變可因不同的病因造成神經退化,臨床上對周邊神經病變的評估多依賴神經傳導檢查,此法固然可以提供神經生理學的資訊,然而對於神經病理及神經退化結果所提供的資訊有限。本研究利用周邊神經病變患者之神經切片,探討周邊神經病變之病理機制以及可能的分子表現 (molecular signatures),用以區分正常與病變之神經,並期許這些發現可以提供解釋各種神經病變可能的機制與原因。
本研究以三種類型之周邊神經病變為研究對象:(1) 發炎型神經病變 (inflammatory neuropathies),主要為慢性脫髓鞘性神經病變 (Chronic inflammatory demyelinating polyneuropathy)、急性神經根炎 (Guillain-Berre syndrome) 及血管炎 (Vasculitis),(2) 軸索退化型神經病變 (neuropathies of axonal degeneration type),(3) 遺傳型神經病變 (hereditary neuropathies),主要為Charcot-Marie-Tooth disease (CMT)。除了以厚片評估神經病理以外,並以免疫化學染色法評估 (1) 巨噬細胞之浸潤、(2) aquaporin 4 (AQP4) 的表現及 (3) Apolipoprotein E (ApoE) 的表現。 以 Iba1 標定巨噬細胞,發現 Iba1(+) 巨噬細胞在正常神經的表現量極低,於軸索退化神經病變及 CMT 患者之神經有些許 Iba1(+) 巨噬細胞,在發炎型神經病變之神經,Iba1(+) 巨噬細胞量大幅增加,經過定量,發炎型神經病變患者之 Iba1(+) 巨噬細胞密度為軸索退化型之四倍 (p < 0.0001),顯示巨噬細胞之浸潤與發炎神經病變之機制與結果有關。 以 AQP4 與 ApoE 進行免疫化學染色,藉以探討這兩個分子的表現是否會因不同的神經病變而有所不同。AQP4 與 ApoE 在軸索退化型神經之神經束膜 (perineurium) 有明顯增加的現象,在正常人的神經束膜上則無任何反應,至於在發炎型神經病變及 CMT 之神經束膜上則可觀察到程度不同的染色。 總結以上的實驗觀察,有以下兩點結論:(1) 發炎型神經病變患者之巨噬細胞的浸潤量會有明顯的增加,(2) AQP4 與 ApoE 在各種神經病變之神經束膜上皆可觀察到增加的現象。這些結果可以提供周邊神經病變之可能病理機制或神經對於退化的反應。 關鍵詞: 發炎型神經病變、軸索退化、巨噬細胞、Iba1、AQP4、ApoE Nerve degeneration in peripheral nerve disorders (peripheral neuropathies) can be caused by different etiologies. Among these neuropathies, the inflammatory type is currently treatable with immunomodulating agents. Thus it is important to explore molecular signatures of immune-mediated injury and axonal degeneration. Clinically neuropathies are usually assessed by nerve conduction studies, which only provide neurophysiological information. This study aimed to study the neuropathology and mechanisms of neuropathies on sural nerve biopsies. Patients with neuropathies were classified into the following groups: (1) inflammatory neuropathies (including chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, and vasculitic neuropathy), (2) neuropathies of axonal degeneration type (degeneration group), and (3) hereditary neuropathies (Charcot-Marie-Tooth disease, the CMT group). The findings were compared with sural nerve biopsies of healthy control subjects (the control group). Sural nerve biopsies were immunostained with the following markers: (1) Iba1 for macrophages, (2) aquaporin 4 (AQP4) for water channel, and (3) apolioproteinE (apoE). In the inflammatory neuropathies group, there were marked Iba1(+)-macrophages. Only mild iba1-immunoreactivities were noted in the degeneration and CMT groups. There was only minimal Iba1(+) cells in the control group. These observations were confirmed by quantitation of the densities of Iba1-immunoreactivities (p < 0.0001), indicating that macrophages play important roles in mechanisms or consequences of inflammatory neuropathies. In the degeneration group, the immunoreactitivies of AQP4 and apoE were upregualted in the perineurium of the degeneration group. The expression of AQP4 and apoE was absent in the control group. There was variable expression of AQP4 and apoE in the perineurium of the inflammatory and CMT groups. In conclusion, macrophages infiltration was increased in the inflammatory group. The expression of AQP4 and ApoE was increased in the perineurium of various forms of neuropathies. These findings may provide potential explanation for the mechanisms and consequences of neuropathies. Key words: inflammatory neuropathy, axonal degeneration, macrophage, Iba1, AQP4, ApoE |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42962 |
Fulltext Rights: | 有償授權 |
Appears in Collections: | 解剖學暨細胞生物學科所 |
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