貝它一型轉形生長因子對犬蛔蟲症肺部損傷與纖維化之分子致病機轉

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Title:	貝它一型轉形生長因子對犬蛔蟲症肺部損傷與纖維化之分子致病機轉 Molecular pathogenesis of TGF-β1 on pulmonary injury and fibrosis of toxocariasis
Authors:	Hung, Yu-Lin
Keywords:	犬蛔蟲;保幼宿主;纖維化;免疫組織化學染色法;西方墨點法;Toxocara canis;Paratenic host;Fibrosis;Immunohistochemistry;Western blot
Date:	2013-06-17
Issue Date:	2018-11-14 09:39:10 (UTC+8)
Abstract:	人類是犬蛔蟲的保幼宿主，當人類不慎誤食犬蛔蟲受孕蟲卵後，幼蟲會於宿主體內移行並不會進一步發育為成蟲，可導致內臟幼蟲移行症，若幼蟲移行至肺部，則可造成肺部受損。目前一些研究指出：犬蛔蟲幼蟲侵入小鼠小腸、肝臟、肌肉或腦部導致肉芽腫性發炎反應，可發現貝它一型轉形生長因子(transforming growth factor-β1, TGF-β1)增強的表現。而許多研究已指出：TGF-β1對於肺部損傷與纖維化扮演重要角色。本研究欲探究於鼠犬蛔蟲症中TGF-β1對於肺部損傷與纖維化的角色。以可抑制TGF-β1表現的胜肽(LSKL)或對照胜肽(SLLK)或生理食鹽水(NS)，自小鼠感染犬蛔蟲後第1天開始，每天2次腹腔注射至感染鼠(2.5 μg/g-weight)，於感染後第2天~83天期間，摘取小鼠肺臟，探討TGF-β1、細胞增生核抗原(Proliferating Cell Nuclear Antigen, PCNA)、S100A12、物質P (Substance P, SP)、嗜酸性球趨化因子(Eotaxin)、Foxp3(forkhead box p3)、組織型麩胺酸轉胺酶(Transglutaminase 2, TG 2)、結締組織生長因子(connective tissue growth factor, CTGF)於肺臟的表現情形，以探討上述因子參與「蛔蟲症肺炎」之分子免疫病理機轉。經由IHC (Immunohistochemistry)及WB (western blot)的實驗結果顯示，受犬蛔蟲感染的小鼠藉LSKL降低TGF-β1的表現，發現相較於SLLK的組別，TGF-β1、PCNA、S100A12、SP、Foxp3、Eotaxin、TG-2、CTGF在長期感染75及83天的組別確實有表現下降的情形，而在IHC的組織切片觀察下，也發現LSKL組鼠，相較於SLLK或NS組，長期感染75及83天的肺臟纖維化程度，有大幅降低的情形，故可推斷肺臟發炎與纖維化程度的減緩應和TGF-β1之表現降低有關。 Human beings are the paratenic host of Toxocara canis and when people accidentally ingest T. canis embryonated eggs, T. canis larvae can not grow further into adult worms then they may migrate in the body thus leading to visceral larva migrans. If larvae reach to the lungs they may cause pulmonary injuries. Some studies have indicated that enhanced expression of transforming growth factor-β1 (TGF-β1) were found during larval invasion of the small intestine, liver, muscle, and the brain of T. canis-infected mice. Moreover, substantial studies indicated that TGF-β1 play an important role in pulmonary injury and fibrosis. Present study intends to explore the role of TGF-β1 in pulmonary injury and fibrosis of pulmonary toxocariasis in mice. Pulmonary injury associated biomarkers expression including TGF-β1, proliferating cell nuclear antigen (PCNA), S100A12, Substance P (SP), eotaxin, Foxp3, transglutaminase 2 (TG 2), and connective tissue growth factor (CTGF) in the lungs were assessed by giving peptide inhibitor (LSKL) of TGF-β1 via peritoneal injection twice (2.5 μg/g-weight/ times) per day in T. canis-infected mice by using immunohistochemistry and western blotting to insight into the molecular pathogenesis of those biomarkers involved in pulmonary toxocariasis. Results indicated that pulmonary injury was lessened in LSKL-treated mice as compared to those in SLLK- or NS-treated mice and it was explained by that reduced TGF-β1 expression is supposed to work with comitant reduction of PCNA, S100A12, SP, Foxp3, Eotaxin, TG 2, and CTGF expressions to synergically contribute to the reduced pulmonary inflammation and fibrosis as found at 75 and 83 days post infection.
Description:	碩士委員-葉光勝委員-李岳倫指導教授-范家堃
Data Type:	thesis
Appears in Collections:	[Graduate Institute of Medical Sciences] Dissertation/Thesis

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