本研究以微型電腦斷層造影儀之影像（這種不具有侵入性、不用犧牲動物、可長期性的監測同一動物，以減少個體差異方法）作為監測巴拉刈所導致之大鼠肺纖維化之情形。成鼠先秤重及Micro-CT造影，再以隨機方式分成控制、低劑量、中劑量、高劑量四組，依其組別給予單次不同劑量之巴拉刈水溶液，給藥後每週進行兩次秤重及Micro-CT造影，連續進行四週，並在每週造影後，每組隨機犧牲一隻成鼠，取出肺臟，進行檢體及組織病理觀察。結果顯示，控制組之肺臟檢體色澤正常，沒有出血，組織病理學則以I型肺泡細胞為主，無間質性肺炎且肺泡完整清淨，肺泡壁薄而完整；實驗組方面，第一~三週肺臟檢體外觀及組織病理的呈現出血點(petechia)及出血病灶且越趨嚴重，第四週則消退，且Micro- CT影像評估亦相同。各劑量之實驗鼠體重隨著巴拉刈劑量的增加，其體重增加量隨之減少，實驗鼠肺臟重量則因巴拉刈劑量的增加隨之增加，所以肺臟重量與體重之比值隨著劑量增加而升高，而經由三維的重建影像顯示隨著巴拉刈劑量的增加，肺部的出血及纖維化亦較為嚴重，因此肺部的有效容積量則逐漸降低。因此，此動物模式可做為診斷及監測肺纖維化之研究模式，而Micro-CT造影可做為診斷及監測的最佳工具之一。

This aim of study is monitoring Paraquat-induced pulmonary fibrosis in rats with Micro-computed tomography (Micro-CT) findings. That is non-invasion and do not need to sacrifice animals, and can supervise the same animals for reduced individual differences. Adult rats were measured body weight and imaged by Micro-CT, then divide into four groups randomly; according to control, low dosage, medium doagse, high dosage. Each group was given aqueous solution of Paraquat via oral single dosage at 0mg/kg, 40mg/kg, 60mg /kg, 80mg/kg, respectively.
In control group, the color and luster of the lung samples appeared normal and no petechia was observed. In histopathology sections showed that alveoli were complete and clear with walls being thin and brittle. In experimental group, some petechia were observed in lung samples , the area of fibroblast and fibrinogen in histopathology sections were found , and the ground-glass predominance and reticulation structure in Micro-CT findings were increased during the period from the 1st week to the 3rd week, and degrade in the 4th week after the administration. In the experimental group, the lung weights of adult rats were increased, with the dosage of paraquat was increased, but the body weight increments of adult rats were decreased, therefore the ratio of lung weights over body weights were increased with dosage, that was matched the results of associated researches.
The Mirco-CT images from 3D reconstruction show that the effective capacity volume of the lung gradually decreased with dosage increased, therefore Micro-CT as a powerful tool for fast diagnosis and longitudinal monitoring of pulmonary fibrosis. It might have more extensive application in the nearly future.

目次
中文摘要--------------------------------------------------i
英文摘要-------------------------------------------------ii
目次----------------------------------------------------iii
圖次-----------------------------------------------------vi
表次-----------------------------------------------------ix
第一章 前言----------------------------------------------01
1-1 微型電腦斷層造影儀-----------------------------------01
1-2 肺纖維化（Pulmonary fibrosis）-----------------------01
1-3 巴拉刈（Paraquat）-----------------------------------03
1-4 研究架構---------------------------------------------05
第二章 文獻探討------------------------------------------06
2-1 研究背景---------------------------------------------06
2-2 巴拉刈之生化機制-------------------------------------08
2-3 肺纖維化之診斷---------------------------------------09
2-4 文獻研究歸納-----------------------------------------09
2-5 評估之依據-------------------------------------------10
第三章 材料與方法----------------------------------------12
3-1 材料-------------------------------------------------12
3-1-1 試驗藥劑-------------------------------------------12
3-1-2 實驗動物-------------------------------------------13
3-1-3 核能研究所研發的動物用錐形射束斷層掃描系統---------13
3-2 方法-------------------------------------------------16
3-2-1 實驗流程-------------------------------------------16
3-2-2 給藥方式-------------------------------------------16
3-2-3 Micro-CT造影---------------------------------------17
3-2-4 實驗鼠之解剖---------------------------------------19
3-2-5 病理切片及染色-------------------------------------19
3-2-6 評估及定量-----------------------------------------20
第四章 結果----------------------------------------------24
4-1 肺部檢體觀察-----------------------------------------24
4-2 成鼠體重的變化---------------------------------------25
4-3 成鼠肺臟重量-----------------------------------------25
4-4 成鼠肺重與體重之比值---------------------------------26
4-5 成鼠組織病理觀察-------------------------------------26
4-6 成鼠Micro-CT影像-------------------------------------28
第五章 討論----------------------------------------------30
5-1 肺臟檢體觀察與成鼠組織病理觀察-----------------------30
5-2 成鼠體重、肺臟重量及成鼠肺臟重量與體重之比值間的關係-31
5-3 成鼠Micro-CT之影像應用於監測肺纖維化之可行性---------33
5-4 綜合討論---------------------------------------------34
參考文獻-------------------------------------------------67
附錄-----------------------------------------------------73
附錄（一）SPF實驗動物------------------------------------73
附錄（二）Hematoxylin & Eosin染色------------------------74
附錄（三）Masson’s Trichrome膠原染色--------------------76

圖 次
圖一: 核研所 Micro-CT造影系統----------------------------36
圖二: 實驗鼠犧牲、灌流、肺臟解剖圖-----------------------37
圖三: Micro-CT造影影像呼吸校正示意圖---------------------38
圖四: Micro-CT造影影像自動圈選示意圖---------------------39
圖五: 肺臟檢體觀察，控制組之肺臟檢體圖-------------------40
圖六: 肺臟檢體觀察，低劑量組之肺臟檢體圖-----------------41
圖七: 肺臟檢體觀察，中劑量組之肺臟檢體圖-----------------42
圖八: 肺臟檢體觀察，高劑量組之肺臟檢體圖-----------------43
圖九: 各劑量之體重增加量之比較圖-------------------------44
圖十: 各個劑量間，在不同時間點的肺臟重量之---------------45
圖十一: 各劑量之肺臟重量之比較圖-------------------------46
圖十二: 各劑量之肺臟重量與體重之比值之比較圖-------------47
圖十三: 控制組之組織病理切片之觀察圖---------------------48
圖十四: 低劑量組 H&E stain之組織病理切片之觀察圖---------49
圖十五: 中劑量組 H&E stain之組織病理切片之觀察圖---------50
圖十六: 高劑量組 H&E stain之組織病理切片之觀察圖---------51
圖十七: 低劑量組 Masson’s stain之組織病理切片之觀察圖---52
圖十八: 中劑量組 Masson’s stain之組織病理切片之觀察圖---53
圖十九: 高劑量組 Masson’s stain之組織病理切片之觀察圖---54
圖二十: 控制組成鼠之Micro-CT肺臟影像---------------------55
圖二十一: 低劑量組成鼠之Micro-CT肺臟影像-----------------56
圖二十二: 中劑量組成鼠之Micro-CT肺臟影像-----------------57
圖二十三: 高劑量組成鼠之Micro-CT肺臟影像-----------------58
圖二十四: 不同劑量肺臟有效容積量減少之比較圖-------------59
圖二十五: 不同劑量Micro-CT的3D定量影像比較圖-------------60

表 次
表一: 本研究動物造影實驗之造影條件-----------------------18
表二: 台灣農藥市場之分類---------------------------------61
表三: 台灣農藥市場主要非選擇性除草劑---------------------62
表四: 前人研究巴拉刈（Paraquat）以動物為研究主體之研究---63
表五: 前人研究巴拉刈（Paraquat）以人類為研究主體之研究---64
表六: 肺組織切片之分級及其特徵---------------------------65
表七: 本研究組織病理切片進行之結果-----------------------66

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