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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蘇霩靄(Kua-Eyre Su) | |
| dc.contributor.author | I-Chuang Wang | en |
| dc.contributor.author | 王以莊 | zh_TW |
| dc.date.accessioned | 2021-06-08T05:56:15Z | - |
| dc.date.copyright | 2008-02-20 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-02-01 | |
| dc.identifier.citation | Alvarez, J.I., Londono, D.P., Alvarez, A.L., Trujillo, J., Jaramillo, M.M., Restrepo, B.I., 2002. Granuloma formation and parasite disintegration in porcine cysticercosis: comparison with human neurocysticercosis. J Comp Pathol 127, 186-193.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/24771 | - |
| dc.description.abstract | 本研究首先建立有鉤絛蟲 (Taenia solium) 與亞洲絛蟲 (T. saginata asiatica) 在近交品系小鼠的感染模式，以作為人類囊蟲病的動物模式 (animal model)。結果顯示，在測試的三種近交品系小鼠 －C3H/HeN(以下簡稱C3H)、C57BL/6與BALB/cAnN中，C3H與C57BL/6小鼠可成功地感染囊蟲，但以前者之蟲體回收率較高。C3H小鼠在感染囊蟲後4到6週時血清中IgG1總量升高，明顯呈現Th2型免疫反應。在C3H小鼠感染豬囊尾蟲6週後，以cDNA微陣列晶片分析比較活囊蟲周邊的組織與未感染的小鼠同部位組織，基因表現之差異，發現在囊蟲的周邊組織中，與發炎或Th1免疫型反應相關的細胞激素下降，而與Th2型反應相關或抑制發炎的因子上升，顯示囊蟲周邊的發炎反應被抑制而且免疫反應傾向Th2型。其中調控Th1型免疫反應的造骨素(osteopontin, OPN) 基因表現更明顯地降低，進一步以RT-PCR半定量分析的結果亦驗證OPN的表現降低。但以藥物praziquantel治療殺死囊蟲而導致其周邊組織發炎，則會大幅的提高OPN基因的表現，顯示活的囊蟲在宿主組織內具有降低OPN基因表現的能力。進一步的以體外細胞培養實驗證實，正常C3H小鼠之白血球 (blood leukocytes)與活囊蟲或囊蟲之排泌性抗原共同培養，白血球的OPN基因表現會降低，並使得IL-12 與IFN-γ亦隨之降低。以ELISA檢測感染囊蟲之C3H小鼠的血液單核球經囊蟲排泌性抗原刺激後細胞激素之產量，發現單核球產生的OPN與IL-12蛋白質的總量會下降，證實囊蟲所產生的排泌性物質會降低單核球OPN的表現，並抑制免疫反應傾向Th1型。再者，若將rmOPN(重組小鼠OPN) 或抗OPN抗體直接注射於移植囊蟲周邊的小鼠組織，接受rmOPN注射的小鼠，其移植囊蟲在四週後全部鈣化，而注射抗OPN抗體的小鼠，其囊蟲周邊之發炎反應則遠低於接受PBS注射的對照組，確認了OPN在囊蟲的肉芽腫發炎或鈣化反應中扮演重要的角色。整體而言，囊蟲可能藉抑制OPN基因之表現降低Th1發炎反應，並藉此機制逃避宿主免疫系統的傷害，因而延長囊蟲在宿主體內存活的時間。 | zh_TW |
| dc.description.abstract | In this study, we tried to use three inbred mice stains, C3H/HeN, C57BL/6 and BALB/cAnN established an animal model of Taenia solium and T. saginata asiatica metacestode infection for human cysticercosis. Worm recovery results demonstrated that C3H/HeN and C57BL/6 strains were able to be infected by injection of oncospheres. Moreover, C3H strain mice exhibited higher worm recovery than C57 mice. Immune response of mice was trended to Th2-type from 4 to 6 weeks post-infection, because the increase in total serum IgG1 level of C3H mice. Microarray analysis of C3H mice tissue surrounding 6-weeks-old viable T. solium cysticerci and tissue at similar location without cysticercus revealed that metacestodes infection led to the decrease in expression of inflammation- and Th1-type response related cytokines, and enhanced anti-inflammatory factors and Th2-type response cytokine expression. Of special interest was the drastic down-regulation in the expression of Osteopontin (OPN) gene. Furthermore, inflammation and granuloma formation in human neurocysticercosis has been attributed to Th1-type immune responses of the host. In the present murine model, over 94% of Taenia solium metacestodes were viable and elicited no granulomatous inflammation whereas parasites killed by praziquantel treatment elicited rapid granuloma formation that calcified within two weeks. OPN is a Th1-related cytokine that is up-stream of IL-12 and which may play an essential role in granuloma formation and calcification. OPN mRNA expression was down-regulated in tissues surrounding viable cysticerci, but was up-regulated in inflammatory tissues surrounding degenerating cysticerci. Moreover, co-culture with a viable cysticercus or excretory/secretory (ES) products from these metacestodes led to a decrease in OPN, IFN-γ, and IL-12 expression whereas co-culture with somatic protein enhanced OPN expression by leukocytes. Addition of recombinant mouse OPN (rmOPN) was able to counteract the down-regulation of IL-12 and IFN-γ mRNA expression, but not OPN mRNA expression in leukocyte cultures. Furthermore, injection of rmOPN into the tissues surrounding implanted cysticerci enhanced inflammatory responses while similar injection of anti-rmOPN antibody reduced inflammation. Suppression of host Th1-type granulomatous inflammation by ES products from T. solium metacestodes is related to down-regulation of OPN gene expression, confirming that OPN plays an important role in inflammation and granuloma formation. In conclusion, metacestodes inhibit Th1-type inflammation via decreasing expression of OPN gene and utilize this mechanism to escape damages caused by host immune response. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T05:56:15Z (GMT). No. of bitstreams: 1 ntu-97-D86445004-1.pdf: 3769638 bytes, checksum: ec15504eb24b8022494a1fe38a895eae (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 題目……………………………………………………………………………….I
口試委員會審定書………………………………………………………………II 誌謝………………………………………………………………………..……III 中文摘要………………………………………………………………..………IV 英文摘要………………………………………………………………………..VI 第一章 緒論………………………………………………..…………………..1 第二章 材料與方法…………………………………………..………………..7 2. 1. 蟲症動物模式之建立…………………………………………………7 2.1.1. 實驗動物..........................................................................................7 2.1.2. 絛蟲的來源與蟲卵之採收法………………………………..……7 2.1.3. 六鉤幼蟲 (oncospheres) 之孵化及動物感染……………………8 2.1.4. 蟲體回收比較……………………………………………………..9 2.1.5. 組織學研究…………………………………………………..……9 2.1.6. C3H小鼠性別與六鉤幼蟲感染數量對囊蟲獲蟲率之影…….....10 2.1.7. 囊蟲排泌性抗原的製備…………………………………...…….10 2.2.豬囊尾蟲抑制宿主Th1型肉芽腫發炎反應之探討…………….……11 2.2.1. 實驗動物……………………………………………...………….11 2.2.2. 有鉤絛蟲的來源…………………………………………...…….11 2.2.3. 六鉤幼蟲之孵化及動物感染…………………...……………….11 2.2.4. 囊蟲周邊小鼠組織的檢體之採取…………………...………….11 2.2.5. 感染小鼠血清中IgG1與IgG2a抗體之偵測……………………11 2.2.6. 基因表現分析……………………………………………..……..12 2.2.7. 囊蟲排泌性抗原與體抗原之製備……………………...……….13 2.2.8. 細胞檢體的備製…………………………………...…………….14 2.2.9. 白血球的共同培養……………………………………..………..14 2.2.10. RNA之萃取與反轉錄…………………………………………..15 2.2.11. 半定量RT-PCR………………………………………………….15 2.2.12. 細胞激素的偵測……………………………..…………………16 2.2.13. 外源性重組小鼠OPN蛋白對宿主發炎反應影響之評估…….17 2.2.14. 統計分析………………………………………………………..17 第三章 結果……………………………………………………………..……..18 3.1. 蟲症動物模式之建立………………………………...………………18 3.1.1. 不同近交品系小鼠對囊蟲感受性之比較………………………18 3.1.2. 感染劑量及C3H小鼠性別對囊蟲回收之影響…………………18 3.1.3. C3H小鼠皮下注射六鉤幼蟲後，平均囊蟲獲蟲數、存活狀況及病理變化之時間序列變化..…..…………..…………...………19 3.2. 豬囊尾蟲抑制宿主Th1型肉芽腫發炎反應之探討…………...……20 3.2.1. 小鼠cDNA微陣列分析……………………………………...…..20 3.2.2. 豬囊尾蟲於C3H小鼠誘發之IgG1與IgG2a抗體的變化……...20 3.2.3. 囊蟲周邊宿主組織OPN基因之表現………………………..….21 3.2.4. 活囊蟲及體抗原對正常小鼠白血球的OPN基因表現之影響...21 3.2.5. 囊蟲排泌性抗原對OPN及IL-12基因表現影響之時間序列變化 ……………………...………………………...………………...…21 3.2.6. 囊蟲排泌性抗原及外源性rmOPN對OPN、IL-12、IFN-γ及其它細胞激素基因表現的影響……………………………...……………22 3.2.7. 囊蟲排泌性抗原及外源性rmOPN對OPN、IL-12、IFN-γ及其它細胞激素基因表現的影響……………………………………...……22 3.2.8. 重組OPN蛋白質及抗rmOPN處理對移植囊蟲周邊組織發炎反應之影響………………………………...………………………………22 3.2.9. 囊蟲排泌性抗原及體抗原對源自感染囊蟲小鼠之單核球生成細胞激素之影響…………………………………...…………………...….23 第四章 討論 ………………………………………………………......………24 圖目錄 Fig. 1…………………………………………………………………………….35 Fig. 2. …………………………………………………………...………………36 Fig. 3…………………………………………….……………………...….……37 Fig. 4…………………………………………….………………………………38 Fig. 5…………………………………………………………….………………39 Fig. 6……………………………………………………….. …………….…….40 Fig. 7…………………………………………………………………………….41 Fig. 8…………………………………………………………………………….42 Fig. 9…………………………………………………………………………….43 Fig. 10……………………………………………………………..…………….44 Fig. 11…………………………………………..……………………………….45 Fig. 12………………………………………………………..………………….46 表目錄 Table 1. ………………………………………………………………………….47 Table 2. ………………………………………………………………………….48 Table 3. ………………………………………………………………………….49 參考文獻…………………………………………………..……………………50 附錄 已發表文章 1. Suppression of host Th1-type granulomatous inflammation by Taenia solium metacestodes is related to down-regulation of osteopontin gene expression 2. Rodent model for long-term maintenance and development of the viable cysticerci of Taenia saginata asiatica 3. Sexual development of Taenia solium in hamsters from rodent-derived cysticerci | |
| dc.language.iso | zh-TW | |
| dc.subject | 亞洲絛蟲 | zh_TW |
| dc.subject | 囊蟲病 | zh_TW |
| dc.subject | 有鉤絛蟲 | zh_TW |
| dc.subject | 造骨素 | zh_TW |
| dc.subject | 豬囊尾蟲 | zh_TW |
| dc.subject | Taenia solium | en |
| dc.subject | cysticercosis | en |
| dc.subject | osteopontin | en |
| dc.subject | cysticerci | en |
| dc.subject | Taenia saginata asiatica | en |
| dc.title | 囊蟲症動物模式之建立及豬囊尾蟲抑制宿主Th1型肉芽腫發炎反應之探討 | zh_TW |
| dc.title | The establishment of an animal model for cysticercosis and studies on down-regulation of Th1-type granulomatous inflammation by metacestodes of Taenia solium | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.coadvisor | 范秉真(Ping-Chin Fan) | |
| dc.contributor.oralexamcommittee | 翁秀貞,李金木,王蓮成 | |
| dc.subject.keyword | 有鉤絛蟲,亞洲絛蟲,豬囊尾蟲,造骨素,囊蟲病, | zh_TW |
| dc.subject.keyword | Taenia solium,Taenia saginata asiatica,cysticerci,osteopontin,cysticercosis, | en |
| dc.relation.page | 60 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2008-02-01 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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