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標題: 以大鼠模式應用磁振造影於肝臟纖維化之研究
MRI Study of Liver Fibrosis in Rat Model
作者: 洪義文
Hung, Yi-Wen
關鍵字: 肝纖維化;Liver fibrosis;磁振造影;MRI
出版社: 獸醫學系暨研究所
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肝纖維化是因肝細胞外基質過度累積所造成,其最主要的成分是膠原蛋白,而嚴重肝纖維化會演變成肝硬化;肝硬化是台灣人民十大死因之一,傳統的確診方法是以肝穿刺為主,但它具侵入性且較具危險性;而磁振造影(Magnetic resonance imaging; MRI)因可提供良好的組織特性、強烈的組織對比、多種切面影像、不具游離輻射及不具侵入性之檢測,其臨床價值是優於其他傳統的影像診斷模式;並可結合超順磁性氧化鐵(Superparamagnetic iron oxide ; SPIO)對比劑之特性,應用於肝臟生理機制之評估;故可藉由大鼠肝纖維化之組織形態上的變化,對應於MRI之組織參數特性的活體研究,來探討有關肝纖維化的MRI參數改變,評估其在肝臟實質病變之臨床診斷價值,並提供組織內不同的成分及彼此間交互作用的訊息,以做為早期診斷的指標。本研究以16、12、8週齡之雄性SD Rat,分別誘導4, 8, 12週為誘導組,並以正常20週齡之雄性SD Rat為對照組(n=8),誘導藥物為50 % CCl4(劑量為2 mL/kg/次/隻);以MRI掃描Rat肝臟,分別計算其T1 & T2 relaxation time及Magnetization transfer ratio(MTR);並於Rat尾靜脈注射SPIO後再掃描,檢測其訊號強度(signal intensity ;SI),以計算其Relative enhancement(RE%);並檢測hepatic kupffer cell吞噬鐵粒子的程度,以評估其活性;動物犧牲時抽血檢測其血液生化值(GOT、GPT),再解剖檢查肉眼及組織病理變化,測量肝、脾臟器官重量/體重之比值,並做肝臟膠原蛋白之定量分析及以西方氏墨點偵測法(western blot)分析α-smooth muscle actin(α-SMA)之表現量,以評估肝纖維化程度與MRI影像訊號之相關性。實驗結果在T1 & T2 relaxation time方面:各誘導組相對於對照組皆有延長的現象,而各誘導組間的差異不大;但誘導12週結束後,讓其病況回復1、2、4、8、15天後,再以MRI掃描,檢測其T1 & T2 relaxation time皆有變短的趨勢,且與對照組無顯著差異。而在MTR方面:誘導4週組相對於對照組有些許下降的趨勢,誘導8週組相對於誘導4週組有回升的趨勢,但誘導12週組相對於誘導8週組其數值的差異不大,推測有可能因肝臟內部仍有些微發炎反應存在,干擾其MT效應所導致;而在回復後,再檢測其MT effect,發現MTR有明顯增高的趨勢。在注射SPIO對比劑後,其對照組的MRI影像呈現明顯黑化,表示Kupffer cell活性很好;誘導4、8、12週組,只有些微的黑化情形,表示Kupffer cell活性明顯降低。綜合實驗結果可知,以MRI並配合對比劑之應用,證實經由CCl4誘導大鼠肝纖維化,且經過15天的回復,使誘導期間的發炎程度趨緩後,其膠原蛋白有明顯的增生,而利用MRI檢測能真正反應出肝纖維化在MRI中的組織特性,其確實不失為一種有效的診斷肝纖維化程度之工具。

Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases, advanced liver fibrosis results in cirrhosis, and liver cirrhosis was one of ten leading causes of death in Taiwan. The conventional method in diagnosis was based on the liver biopsy, but this method was invasive and not cost-effective. Magnetic resonance imaging (MRI) is a non-invasive diagnostic modality, with the advantages of non-ionizing radiation, high sensitivity and specificity in tissue characterization, and that technology feasible and provided the distinct tissue contrast in anatomic structure and obtained the imagings in multiple slices. The clinical performance of MRI is superior to other conventional imaging modalities. In this experiment, we tried to explode the MRI findings of liver fibrosis in rats induced by oral administration of CCl4 for various durations(4, 8 and 12wks). Serum biochemicological and histopathological studies were also performed before and after sacrifice of rats. The results showed significant prolongation of both T1 and T2 relaxation times, higher magnetization transfer(MT)indices in fibrotic rat livers. After intravenous administration of superparamagnetic iron oxide (SPIO)liver-specific contrast agent, the descent of signal attenuation of hepatic parenchyma in the disease rat liver expressed the impairment of the cellular activity of Kupffer cells in rat liver. In conclusion, MRI is a potentially powerful technique for diagnosing fibrotic liver diseases.
其他識別: U0005-2308200718460100
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