跳到主要內容

臺灣博碩士論文加值系統

(3.235.227.117) 您好!臺灣時間:2021/08/01 23:27
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:陳俊升
研究生(外文):Jiun-Sheng Chen
論文名稱:中醫傳統草藥方劑-龍膽瀉肝湯變方用於大鼠急性肝損傷模式之解毒與抗氧化療效評估
論文名稱(外文):The Evaluation of Antioxidation and Detoxification of Traditional Chinese Herbal Drug – Modified Long-Dan-Xie-Gan-Tang in Acute Hepatic Injury Rat Model
指導教授:曾惠芬曾惠芬引用關係邱雲棕邱雲棕引用關係
指導教授(外文):Huey-Fen TzengYung-Tsung Chiu
學位類別:碩士
校院名稱:國立暨南國際大學
系所名稱:生物醫學科技研究所
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:64
中文關鍵詞:龍膽瀉肝湯急性肝損傷動物模式細胞色素P450抗氧化
外文關鍵詞:Long-Dan-Xie-Gan-Tangrat acute liver injury modelcytochrome P450antioxidation
相關次數:
  • 被引用被引用:0
  • 點閱點閱:444
  • 評分評分:
  • 下載下載:132
  • 收藏至我的研究室書目清單書目收藏:0
龍膽瀉肝湯為中國傳統方劑,廣泛的應用在急性肝炎、膽道炎及膀胱炎等疾病上,本研究利用大鼠急性肝損傷模式來評估龍膽瀉肝湯變方應用於保肝及抗氧化效果,大鼠共分為六組分別為正常對照組、四氯化碳組、低劑量中藥控制組、高劑量中藥控制組、低劑量中藥四氯化碳組及高劑量中藥四氯化碳組(111 and 333 mg/kg)。餵食中藥組預先餵食低、高劑量龍膽瀉肝湯變方七天,第八天再依照各組設計,以50 %四氯化碳(2 ml/kg)誘導肝損傷。利用血清生化值檢查(AST、ALT)、組織切片檢查、西方墨點法分析細胞色素P450相關亞型(2E1、3A1及3A2)表現量、抗氧化酵素(superoxide dismutase, SOD、catalase, CAT、glutathione peroxidase, GPx)以及麩胱甘肽硫轉移酶(glutathione S-transferase)活性測量等,來探討龍膽瀉肝湯變方之藥理機制;再以clone 9細胞株試驗來驗證動物模式之結果。實驗結果發現在高劑量中藥處理組中ALT酵素量顯著高於四氯化碳組(716.6 ± 704.0, 216.6 ± 138.2 IU/l)(P<0.05),組織學中亦發現中藥處理組之空泡樣變性程度較四氯化碳組嚴重,表示龍膽瀉肝湯變方會增強四氯化碳之肝毒性。此外,與正常對照組比較下,中藥控制組細胞色素CYP 2E1、3A1與3A2亞型之表現量顯著上升,抗氧化酵素SOD及GPx活性下降。在中藥處理組亦可觀察到Phase I之CYP 3A1與3A2酵素表現量較四氯化碳組高,其他抗氧化酵素和Phase II酵素GST則無顯著影響。在細胞實驗中龍膽瀉肝湯變方刺激CYP 2E1表現量增加,且無法有效降低氧化壓力;與動物實驗結果相符。故推測服用龍膽瀉肝湯變方後,由於Phase I酵素P450表現量增加、且減低GPx、SOD活性,導致四氯化碳造成之肝毒性加劇。
Long-Dan-Xie-Gan-Tang (LDXGT), a traditional herbal drug, is widely used in various diseases, such as acute hepatitis,cholangitis and cystitis. We investigated the detoxification and antioxidative effects of modified LDXGT in rat acute liver injury model. Rats were grouped into six groups: Control, CCl4, drug-Ctrl (111 and 333 mg/kg) and drug-CCl4 groups. Groups which pretreated with LDXGT for 7 consecutive days were administered either with or without 50 % CCl4 (2 ml/kg) to induce liver injury. The detoxification and antioxidative effects were evaluated by serological tests (AST and ALT), pathological observation, the content of cytochrome P450 (CYP) subfamilies (2E1, 3A1 and 3A2), and the activities of anti-oxidative enzymes (superoxide dismutase; SOD, catalase; CAT, glutathione peroxidase; GPx) and glutathione S-transferase (GST). Moreover, clone 9 cells were used to confirm the pharmacologic effect of LDXGT. The ALT levels of drug-CCl4 groups were significantly higher than those of CCl4 group (716.6 ± 704.0, 216.6 ± 138.2 IU/l). In pathological observation, the level of ballooning degeneration in drug-CCl4 group was higher than that in CCl4 group. It indicates that LDXGT increases the toxicity of CCl4 in the rat model. Besides, the content of CYP subfamilies (CYP 2E1, CYP 3A1, CYP 3A2) were elevated while the activities of GPx and SOD were markedly decreased in drug-Ctrl groups compared with Control group. The drug-CCl4 groups also showed higher CYP subfamilies expression than CCl4 group; however, the enzymes of oxidative defense system and GST were not affected. Our data from in vitro experiments showed that LDXGT was able to induced CYP2E1 overexpression in clone 9 cells but not effective against oxidative stress, which is identical with that from animal studies. It suggests that LDXGT enhances the toxicity of CCl4 perhaps by increasing the content of CYP subfamilies and decreasing the activities of GPx and SOD.
中文摘要 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - I
英文摘要 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -II
目錄- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - IV
表次 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - VIII
圖次 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - IX
第一章 緒論 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 1
1.1 肝臟生理功能簡介 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 2
1.2 肝臟之外來物代謝系統(藥物代謝系統)- - - - - - - - - - - - - - - - - - - - - - - - 4
1.2.1 Phase I官能基化(Functionalization)- - - - - - - - - - - - - - - - - - - - - - - - - 5
1.2.1.1 氧化還原酵素- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 5
1.2.1.1.1 細胞色素P450(Cytochrome P450)- - - - - - - - - - - - - - - - - - - 5
1.2.1.1.2 黃素單氧化酶(Flavin-containing monooxygenases, FMO)- - - 6
1.2.1.1.3 環氧化酶(Cyclooxygenases, COX)- - - - - - - - - - - - - - - - - - - 7
1.2.1.1.4 單胺氧化酶(Monoamine oxidases, MAO)- - - - - - - - - - - - - - 7
1.2.1.1.5 去氫酶及還原酶(Dehydrogenases and Reductase)- - - - - - - - 8
1.2.1.2 水解酵素(Hydrolases)- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 8
1.2.1.2.1 酯酶及胺脢(Esterases and Amidases)- - - - - - - - - - - - - - - - - 8
1.2.1.2.2 環氧水解酶(Epoxide hydrolases)- - - - - - - - - - - - - - - - - - - - 9
1.2.2 Phase II 鍵結反應(Conjugation)- - - - - - - - - - - - - - - - - - - - - - - - - - - 9
1.2.2.1 醣基化(Glucuronidation) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 9
1.2.2.2 穀胱甘肽結合反應- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 10
1.2.2.3 甲基化- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 10
1.2.2.4 乙基化- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 10
1.2.2.5 胺基酸鍵鍵結- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 11
1.3 抗氧化防禦系統 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 11
1.3.1 酵素型抗氧化物(Enzymatic antioxidants)- - - - - - - - - - - - - - - - - - - - 12
1.3.1.1 超氧化物歧化酶(Superoxide Dismutase, SOD)- - - - - - - - - - - - - 12
1.3.1.2 過氧化氫酶(Catalase, CAT)- - - - - - - - - - - - - - - - - - - - - - - - - - 13
1.3.1.3 麩胱甘肽過氧化酶(Glutathione Peroxidase, GPx)- - - - - - - - - - - 14
1.3.2 非酵素形抗氧化物(Non-enzymatic Antioxidants)- - - - - - - - - - - - - - 15
1.3.2.1 維他命 A - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 15
1.3.2.2 維他命 C - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 15
1.3.2.3 維他命 E - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 15
1.3.2.4 礦物質 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 16
1.4藥物導致急性肝損傷- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -16
1.5 急性肝損傷動物模式 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 17
1.5.1 四氯化碳代謝路徑 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 17
1.5.2 四氯化碳所造成肝臟損傷 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 17
1.5.3 脂質過氧化作用(Lipid peroxidation)- - - - - - - - - - - - - - - - - - - - - - - - 18
1.6 龍膽瀉肝湯於中醫之應用 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 18
1.7 研究目的- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 20
第二章 材料與方法 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 21
2.1 實驗材料 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 21
2.1.1 實驗動物 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 21
2.1.2 細胞株與細胞培養- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 21
2.1.3 藥品配製 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 21
2.1.3.1 龍膽瀉肝湯變方的配製- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 21
2.1.3.2 四氯化碳配製及劑量 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 22
2.2 實驗方法 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 22
2.2.1動物實驗- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 22
2.2.1.1 實驗分組 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 22
2.2.1.2 藥物投予方式及實驗流程 - - - - - - - - - - - - - - - - - - - - - - - - - - - 23
2.2.1.3 肝臟組織研磨處理 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 24
2.2.1.4 蛋白質定量 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 24
2.2.1.5 脂質過氧化(Lipid peroxidation)程度分析 - - - - - - - - - - - - - - 25
2.2.1.6 過氧化氫酶(CAT)活性測定 - - - - - - - - - - - - - - - - - - - - - - - - 25
2.2.1.7 麩胱甘肽過氧化酶(GPx)活性測定- - - - - - - - - - - - - - - - - - - - 26
2.2.1.8 超氧化物歧化酶(SOD)活性測定 - - - - - - - - - - - - - - - - - - - - 26
2.2.1.9 麩胱甘肽硫轉移酶(GST)活性測定- - - - - - -- - - - - - -- - - - - - 27
2.2.1.10 西方墨點法分析CYP 2E1、3A1及3A2亞型表現量- - - - - - - - 27
2.2.1.11 血液生化值測定 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -- 28
2.2.1.12 肝臟組織病理學觀察- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 29
2.2.2細胞實驗設計- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 29
2.2.2.1藥物處理方式及流程- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 29
2.2.2.2蛋白質萃取- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 30
2.2.2.3西方墨點法分析細胞色素P450表現量- - - - - - - - - - - - - - - - - - - 30
2.2.2.4脂質過氧化程度分析- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 30
2.2.3 統計分析- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 30
第三章 結果 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 31
3.1 血液生化值檢測 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 31
3.2 組織病理學檢查及評分 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 31
3.3 龍膽瀉肝湯調控細胞色素P450亞型表現量- - - - - - - - - - - - - - - - - - - - - 32
3.4 GST酵素活性測定 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 32
3.5 抗氧化防禦系統活性檢測 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 32
3.6 脂質過氧化指標(Malonlaldehyde, MDA)濃度檢測 - - - - - - - - - - - - - - 33
3.7龍膽瀉肝湯變方對clone 9 細胞株細胞色素P450表現量之影響- - - - - - - 33
3.8龍膽瀉肝湯變方對clone 9細胞株抗氧化壓力之影響- - - - - - - - - - - - - - - 34
第四章 討論 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 35
第五章 結論 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 40
圖表 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 41
附錄一 Lysis buffer 配製 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 50
附錄二 Western blot 材料配置 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 51
參考文獻 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 53
[1]Chang MH, Chen CJ, Lai MS, Hsu HM, Wu TC, Kong MS, Liang DC, Shau WY, Chen DS. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med 1997;336 (26):1855-9.
[2]Lee WM. Drug-induced hepatotoxicity. N Engl J Med 2003;349 (5):474-85.
[3]Clay KD, Hanson JS, Pope SD, Rissmiller RW, Purdum PP, 3rd, Banks PM. Brief communication: severe hepatotoxicity of telithromycin: three case reports and literature review. Ann Intern Med 2006;144 (6):415-20.
[4]Pishvaian AC, Trope BW, Lewis JH. Drug-induced liver disease in 2003. Curr Opin Gastroenterol 2004;20 (3):208-19.
[5]Ernst E, Pittler MH. Risks associated with herbal medicinal products. Wien Med Wochenschr 2002;152 (7-8):183-9.
[6]Schiano TD. Hepatotoxicity and complementary and alternative medicines. Clin Liver Dis 2003;7 (2):453-73.
[7]Michalopoulos GK, DeFrances MC. Liver regeneration. Science 1997;276 (5309):60-6.
[8]Tukey RH, Strassburg CP. Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu Rev Pharmacol Toxicol 2000;40:581-616.
[9]vanDeWater L, Carr JM, Aronson D, McDonagh J. Analysis of elevated fibrin(ogen) degradation product levels in patients with liver disease. Blood 1986;67 (5):1468-73.
[10]Schumann RR, Kirschning CJ, Unbehaun A, Aberle HP, Knope HP, Lamping N, Ulevitch RJ, Herrmann F. The lipopolysaccharide-binding protein is a secretory class 1 acute-phase protein whose gene is transcriptionally activated by APRF/STAT/3 and other cytokine-inducible nuclear proteins. Mol Cell Biol 1996;16 (7):3490-503.
[11]Castell JV, Gomez-Lechon MJ, David M, Fabra R, Trullenque R, Heinrich PC. Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6. Hepatology 1990;12 (5):1179-86.
[12]Meyer UA. Overview of enzymes of drug metabolism. J Pharmacokinet Biopharm 1996;24 (5):449-59.
[13]Xu C, Li CY, Kong AN. Induction of phase I, II and III drug metabolism/transport by xenobiotics. Arch Pharm Res 2005;28 (3):249-68.
[14]Yan Z, Caldwell GW. Metabolism profiling, and cytochrome P450 inhibition & induction in drug discovery. Curr Top Med Chem 2001;1 (5):403-25.
[15]Mandl J, Banhegyi G, Kalapos MP, Garzo T. Increased oxidation and decreased conjugation of drugs in the liver caused by starvation. Altered metabolism of certain aromatic compounds and acetone. Chem Biol Interact 1995;96 (2):87-101.
[16]Siest G, Batt AM, Fournel-Gigleux S, Galteau MM, Wellman-Bednawska M, Minn A, Costesec AA. Induction of plasma and tissue enzymes by drugs: significance in toxicological studies. Xenobiotica 1988;18 Suppl 1:21-34.
[17]Omura T, Sato R. The Carbon Monoxide-Binding Pigment of Liver Microsomes. I. Evidence for Its Hemoprotein Nature. J Biol Chem 1964;239:2370-8.
[18]Ingelman-Sundberg M, Oscarson M, Daly AK, Garte S, Nebert DW. Human cytochrome P-450 (CYP) genes: a web page for the nomenclature of alleles. Cancer Epidemiol Biomarkers Prev 2001;10 (12):1307-8.
[19]Aklillu E, Carrillo JA, Makonnen E, Hellman K, Pitarque M, Bertilsson L, Ingelman-Sundberg M. Genetic polymorphism of CYP1A2 in Ethiopians affecting induction and expression: characterization of novel haplotypes with single-nucleotide polymorphisms in intron 1. Mol Pharmacol 2003;64 (3):659-69.
[20]Gonzalez FJ, Nebert DW. Evolution of the P450 gene superfamily: animal-plant 'warfare', molecular drive and human genetic differences in drug oxidation. Trends Genet 1990;6 (6):182-6.
[21]Lewis DF, Pratt JM. The P450 catalytic cycle and oxygenation mechanism. Drug Metab Rev 1998;30 (4):739-86.
[22]White RE, Manitpisitkul P. Pharmacokinetic theory of cassette dosing in drug discovery screening. Drug Metab Dispos 2001;29 (7):957-66.
[23]Hauswirth JW, Brizuela BS. The differential effects of chemical carcinogens on vitamin A status and on microsomal drug metabolism in normal and vitamin A-deficient rats. Cancer Res 1976;36 (6):1941-6.
[24]Cashman JR. Human flavin-containing monooxygenase: substrate specificity and role in drug metabolism. Curr Drug Metab 2000;1 (2):181-91.
[25]Boolbol SK, Dannenberg AJ, Chadburn A, Martucci C, Guo XJ, Ramonetti JT, Abreu-Goris M, Newmark HL, Lipkin ML, DeCosse JJ, Bertagnolli MM. Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis. Cancer Res 1996;56 (11):2556-60.
[26]Williams CS, Mann M, DuBois RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 1999;18 (55):7908-16.
[27]Kwan SW, Bergeron JM, Abell CW. Molecular properties of monoamine oxidases A and B. Psychopharmacology (Berl) 1992;106 Suppl:S1-5.
[28]Shih JC, Chen K, Ridd MJ. Role of MAO A and B in neurotransmitter metabolism and behavior. Pol J Pharmacol 1999;51 (1):25-9.
[29]Jalkanen S, Salmi M. Cell surface monoamine oxidases: enzymes in search of a function. Embo J 2001;20 (15):3893-901.
[30]Vasiliou V, Pappa A, Petersen DR. Role of aldehyde dehydrogenases in endogenous and xenobiotic metabolism. Chem Biol Interact 2000;129 (1-2):1-19.
[31]Belinsky M, Jaiswal AK. NAD(P)H:quinone oxidoreductase1 (DT-diaphorase) expression in normal and tumor tissues. Cancer Metastasis Rev 1993;12 (2):103-17.
[32]Bort R, Ponsoda X, Carrasco E, Gomez-Lechon MJ, Castell JV. Comparative metabolism of the nonsteroidal antiinflammatory drug, aceclofenac, in the rat, monkey, and human. Drug Metab Dispos 1996;24 (9):969-75.
[33]Jamis-Dow CA, Katki AG, Collins JM, Klecker RW. Rifampin and rifabutin and their metabolism by human liver esterases. Xenobiotica 1997;27 (10):1015-24.
[34]Williams FM. Clinical significance of esterases in man. Clin Pharmacokinet 1985;10 (5):392-403.
[35]Cesaratto L, Vascotto C, Calligaris S, Tell G. The importance of redox state in liver damage. Ann Hepatol 2004;3 (3):86-92.
[36]Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ. Mechanisms of hepatotoxicity. Toxicol Sci 2002;65 (2):166-76.
[37]McCord JM, Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 1969;244 (22):6049-55.
[38]B Halliwell JG. Free radicals in biology and medicine. 1989.
[39]Emerit J, Michelson AM. [Free radicals in medicine and biology]. Sem Hop 1982;58 (45):2670-5.
[40]Chance B. The spectra of the enzyme-substrate complexes of catalase and peroxidase. Arch Biochem Biophys 1952;41 (2):404-15.
[41]Chance B, Oshino N. Kinetics and mechanisms of catalase in peroxisomes of the mitochondrial fraction. Biochem J 1971;122 (2):225-33.
[42]Gaetani GF, Galiano S, Canepa L, Ferraris AM, Kirkman HN. Catalase and glutathione peroxidase are equally active in detoxification of hydrogen peroxide in human erythrocytes. Blood 1989;73 (1):334-9.
[43]Percy ME. Catalase: an old enzyme with a new role? Can J Biochem Cell Biol 1984;62 (10):1006-14.
[44]Wieacker P, Mueller CR, Mayerova A, Grzeschik KH, Ropers HH. Assignment of the gene coding for human catalase to the short arm of chromosome 11. Ann Genet 1980;23 (2):73-7.
[45]Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70 (1):158-69.
[46]Chada S, Whitney C, Newburger PE. Post-transcriptional regulation of glutathione peroxidase gene expression by selenium in the HL-60 human myeloid cell line. Blood 1989;74 (7):2535-41.
[47]Ciriolo MR, Fiskin K, De Martino A, Corasaniti MT, Nistico G, Rotilio G. Age-related changes in Cu,Zn superoxide dismutase, Se-dependent and -independent glutathione peroxidase and catalase activities in specific areas of rat brain. Mech Ageing Dev 1991;61 (3):287-97.
[48]Buettner GR. The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate. Arch Biochem Biophys 1993;300 (2):535-43.
[49]Machlin LJ, Bendich A. Free radical tissue damage: protective role of antioxidant nutrients. Faseb J 1987;1 (6):441-5.
[50]Bissell DM, Gores GJ, Laskin DL, Hoofnagle JH. Drug-induced liver injury: mechanisms and test systems. Hepatology 2001;33 (4):1009-13.
[51]Kaplowitz N. Drug-induced liver injury. Clin Infect Dis 2004;38 Suppl 2:S44-8.
[52]Noguchi T, Fong KL, Lai EK, Alexander SS, King MM, Olson L, Poyer JL, McCay PB. Specificity of a phenobarbital-induced cytochrome P-450 for metabolism of carbon tetrachloride to the trichloromethyl radical. Biochem Pharmacol 1982;31 (5):615-24.
[53]Nastainczyk W, Ahr HJ, Ullrich V. The reductive metabolism of halogenated alkanes by liver microsomal cytochrome P450. Biochem Pharmacol 1982;31 (3):391-6.
[54]Hughes HM, George IM, Evans JC, Rowlands CC, Powell GM, Curtis CG. The role of the liver in the production of free radicals during halothane anaesthesia in the rat. Quantification of N-tert-butyl-alpha-(4- nitrophenyl)nitrone (PBN)-trapped adducts in bile from halothane as compared with carbon tetrachloride. Biochem J 1991;277 ( Pt 3):795-800.
[55]Williams AT, Burk RF. Carbon tetrachloride hepatotoxicity: an example of free radical-mediated injury. Semin Liver Dis 1990;10 (4):279-84.
[56]Recknagel RO, Litteria M. Biochemical changes in carbon tetrachloride fatty liver: concentration of carbon tetrachloride in liver and blood. Am J Pathol 1960;36:521-31.
[57]Recknagel RO, Ghoshal AK. Lipoperoxidation of rat liver microsomal lipids induced by carbon tetrachloride. Nature 1966;210 (5041):1162-3.
[58]Slater TF, Cheeseman KH, Ingold KU. Carbon tetrachloride toxicity as a model for studying free-radical mediated liver injury. Philos Trans R Soc Lond B Biol Sci 1985;311 (1152):633-45.
[59]Lutz LM, Glende EA, Jr., Recknagel RO. Protection by diethyldithiocarbamate against carbon tetrachloride lethality in rats and against carbon tetrachloride-induced lipid peroxidation in vitro. Biochem Pharmacol 1973;22 (14):1729-34.
[60]Smuckler EA, Iseri OA, Benditt EP. An intracellular defect in protein synthesis induced by carbon tetrachloride. J Exp Med 1962;116:55-72.
[61]de Groot H, Noll T. The crucial role of low steady state oxygen partial pressures in haloalkane free-radical-mediated lipid peroxidation. Possible implications in haloalkane liver injury. Biochem Pharmacol 1986;35 (1):15-9.
[62]Recknagel RO, Glende EA, Jr., Dolak JA, Waller RL. Mechanisms of carbon tetrachloride toxicity. Pharmacol Ther 1989;43 (1):139-54.
[63]Haase G, Dunkley WL. Ascorbic acid and copper in linoleate oxidation. I. Measurement of oxidation by ultraviolet spectrophotometry and the thiobarbituric acid test. J Lipid Res 1969;10 (5):555-60.
[64]Recknagel RO, Glende EA, Jr. Spectrophotometric detection of lipid conjugated dienes. Methods Enzymol 1984;105:331-7.
[65]McCay PB, Lai EK, Poyer JL, DuBose CM, Janzen EG. Oxygen- and carbon-centered free radical formation during carbon tetrachloride metabolism. Observation of lipid radicals in vivo and in vitro. J Biol Chem 1984;259 (4):2135-43.
[66]Wade CR, van Rij AM. Plasma thiobarbituric acid reactivity: reaction conditions and the role of iron, antioxidants and lipid peroxy radicals on the quantitation of plasma lipid peroxides. Life Sci 1988;43 (13):1085-93.
[67]Lawrence GD, Cohen G. Ethane exhalation as an index of in vivo lipid peroxidation: concentrating ethane from a breath collection chamber. Anal Biochem 1982;122 (2):283-90.
[68]劉美荷. 龍膽瀉肝湯臨床應用體會. Chinese Journal of Information on Traditional Chinese Medicine 2002;9 (7):63-.
[69]熊益群, 高偉. 龍膽瀉肝湯組成與肝炎一般治則探討. Joural of hubel college of tradioional chinese medicine 1999;1 (3): 44.
[70]Mengs U, Stotzem CD. Renal toxicity of aristolochic acid in rats as an example of nephrotoxicity testing in routine toxicology. Arch Toxicol 1993;67 (5):307-11.
[71]Lin CC, Huang PC, Lin JM. Antioxidant and hepatoprotective effects of Anoectochilus formosanus and Gynostemma pentaphyllum. Am J Chin Med 2000;28 (1):87-96.
[72]Chan TY, Chan JC, Tomlinson B, Critchley JA. Chinese herbal medicines revisited: a Hong Kong perspective. Lancet 1993;342 (8886-8887):1532-4.
[73]Graham-Brown R. Toxicity of Chinese herbal remedies. Lancet 1992;340 (8820):673-4.
[74]Perharic-Walton L, Murray V. Toxicity of Chinese herbal remedies. Lancet 1992;340 (8820):674.
[75]McRae CA, Agarwal K, Mutimer D, Bassendine MF. Hepatitis associated with Chinese herbs. Eur J Gastroenterol Hepatol 2002;14 (5):559-62.
[76]陳奇. 中藥藥理研究方法學. 1993.
[77]Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-54.
[78]Carbonneau MA, Peuchant E, Sess D, Canioni P, Clerc M. Free and bound malondialdehyde measured as thiobarbituric acid adduct by HPLC in serum and plasma. Clin Chem 1991;37 (8):1423-9.
[79]Erdelmeier I, Gerard-Monnier D, Yadan JC, Chaudiere J. Reactions of N-methyl-2-phenylindole with malondialdehyde and 4-hydroxyalkenals. Mechanistic aspects of the colorimetric assay of lipid peroxidation. Chem Res Toxicol 1998;11 (10):1184-94.
[80]Aebi H. Catalase in vitro. Methods Enzymol 1984;105:121-6.
[81]Lawrence RA, Burk RF. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 1976;71 (4):952-8.
[82]Spitz DR, Oberley LW. An assay for superoxide dismutase activity in mammalian tissue homogenates. Anal Biochem 1989;179 (1):8-18.
[83]Chen WJ, Graminski GF, Armstrong RN. Dissection of the catalytic mechanism of isozyme 4-4 of glutathione S-transferase with alternative substrates. Biochemistry 1988;27 (2):647-54.
[84]Ruwart MJ, Wilkinson KF, Rush BD, Vidmar TJ, Peters KM, Henley KS, Appelman HD, Kim KY, Schuppan D, Hahn EG. The integrated value of serum procollagen III peptide over time predicts hepatic hydroxyproline content and stainable collagen in a model of dietary cirrhosis in the rat. Hepatology 1989;10 (5):801-6.
[85]Barker CW, Fagan JB, Pasco DS. Down-regulation of P4501A1 and P4501A2 mRNA expression in isolated hepatocytes by oxidative stress. J Biol Chem 1994;269 (6):3985-90.
[86]Long-Yuan Wu H-PH, Yi-Shin Chen, Nai-Nu Lin, Wan-Chuan Chen,Zheng-Huang Cheng, Wen-Huang Peng and Yung-Tsung Chiu*. Studies on the therapeutic effects of deviated Long-Dan -Xia-Gan-Tang on dimethylnitrosamine induced hepatic damage in rats. J Chin Med 2003;14 (4):205-15.
[87]Yokogawa K, Watanabe M, Takeshita H, Nomura M, Mano Y, Miyamoto K. Serum aminotransferase activity as a predictor of clearance of drugs metabolized by CYP isoforms in rats with acute hepatic failure induced by carbon tetrachloride. Int J Pharm 2004;269 (2):479-89.
[88]Brattin WJ, Glende EA, Jr., Recknagel RO. Pathological mechanisms in carbon tetrachloride hepatotoxicity. J Free Radic Biol Med 1985;1 (1):27-38.
[89]Brautbar N, Williams J, 2nd. Industrial solvents and liver toxicity: risk assessment, risk factors and mechanisms. Int J Hyg Environ Health 2002;205 (6):479-91.
[90]Sugiyama T, Nagata J, Yamagishi A, Endoh K, Saito M, Yamada K, Yamada S, Umegaki K. Selective protection of curcumin against carbon tetrachloride-induced inactivation of hepatic cytochrome P450 isozymes in rats. Life Sci 2006;78 (19):2188-93.
[91]Qin LQ, Wang PY, Wang Y, Kaneko T, Hoshi K, Sato A. Voglibose potentiates the hepatotoxicity of carbon tetrachloride and acetaminophen by inducing CYP2E1 in rats. Hepatol Res 2005;33 (1):50-6.
[92]Song BJ. Ethanol-inducible cytochrome P450 (CYP2E1): biochemistry, molecular biology and clinical relevance: 1996 update. Alcohol Clin Exp Res 1996;20 (8 Suppl):138A-46A.
[93]Dupont I, Lucas D, Clot P, Menez C, Albano E. Cytochrome P4502E1 inducibility and hydroxyethyl radical formation among alcoholics. J Hepatol 1998;28 (4):564-71.
[94]Cohen SD, Khairallah EA. Selective protein arylation and acetaminophen-induced hepatotoxicity. Drug Metab Rev 1997;29 (1-2):59-77.
[95]Reid AB, Kurten RC, McCullough SS, Brock RW, Hinson JA. Mechanisms of acetaminophen-induced hepatotoxicity: role of oxidative stress and mitochondrial permeability transition in freshly isolated mouse hepatocytes. J Pharmacol Exp Ther 2005;312 (2):509-16.
[96]Emery MG, Fisher JM, Chien JY, Kharasch ED, Dellinger EP, Kowdley KV, Thummel KE. CYP2E1 activity before and after weight loss in morbidly obese subjects with nonalcoholic fatty liver disease. Hepatology 2003;38 (2):428-35.
[97]Chalasani N, Gorski JC, Asghar MS, Asghar A, Foresman B, Hall SD, Crabb DW. Hepatic cytochrome P450 2E1 activity in nondiabetic patients with nonalcoholic steatohepatitis. Hepatology 2003;37 (3):544-50.
[98]Wang PY, Kaneko T, Tsukada H, Nakano M, Nakajima T, Sato A. Time courses of hepatic injuries induced by chloroform and by carbon tetrachloride: comparison of biochemical and histopathological changes. Arch Toxicol 1997;71 (10):638-45.
[99]Zhu M, Lin KF, Yeung RY, Li RC. Evaluation of the protective effects of Schisandra chinensis on Phase I drug metabolism using a CCl4 intoxication model. J Ethnopharmacol 1999;67 (1):61-8.
[100]Sheweita SA, Abd El-Gabar M, Bastawy M. Carbon tetrachloride-induced changes in the activity of phase II drug-metabolizing enzyme in the liver of male rats: role of antioxidants. Toxicology 2001;165 (2-3):217-24.
[101]O'Brien M, Kruh GD, Tew KD. The influence of coordinate overexpression of glutathione phase II detoxification gene products on drug resistance. J Pharmacol Exp Ther 2000;294 (2):480-7.
[102]Wei YH. Oxidative stress and mitochondrial DNA mutations in human aging. Proc Soc Exp Biol Med 1998;217 (1):53-63.
[103]Szymonik-Lesiuk S, Czechowska G, Stryjecka-Zimmer M, Slomka M, Madro A, Celinski K, Wielosz M. Catalase, superoxide dismutase, and glutathione peroxidase activities in various rat tissues after carbon tetrachloride intoxication. J Hepatobiliary Pancreat Surg 2003;10 (4):309-15.
[104]Simile MM, Banni S, Angioni E, Carta G, De Miglio MR, Muroni MR, Calvisi DF, Carru A, Pascale RM, Feo F. 5'-Methylthioadenosine administration prevents lipid peroxidation and fibrogenesis induced in rat liver by carbon-tetrachloride intoxication. J Hepatol 2001;34 (3):386-94.
[105]Jung K, Henke W. Developmental changes of antioxidant enzymes in kidney and liver from rats. Free Radic Biol Med 1996;20 (4):613-7.
[106]Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 1991;11 (1):81-128.
[107]Hartley DP, Kolaja KL, Reichard J, Petersen DR. 4-Hydroxynonenal and malondialdehyde hepatic protein adducts in rats treated with carbon tetrachloride: immunochemical detection and lobular localization. Toxicol Appl Pharmacol 1999;161 (1):23-33.
[108]Weidauer E, Lehmann T, Ramisch A, Rohrdanz E, Foth H. Response of rat alveolar type II cells and human lung tumor cells towards oxidative stress induced by hydrogen peroxide and paraquat. Toxicol Lett 2004;151 (1):69-78.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
1. 許詩旺、黃義良(2003)。國民小學教育人員對行銷策略認知及其運作之研究。人文及社會學科教學通訊,14(3),37-53。
2. 許詩旺、黃義良(2003)。國民小學教育人員對行銷策略認知及其運作之研究。人文及社會學科教學通訊,14(3),37-53。
3. 張茂源(2004)。淺析國民小學的自我行銷。研習資訊,21(6),85-89。
4. 張茂源(2004)。淺析國民小學的自我行銷。研習資訊,21(6),85-89。
5. 張芳全(2006)。一九九四年以降之台灣教育改革分析。教育資料與研究雙月刊,68,221-240。
6. 張芳全(2006)。一九九四年以降之台灣教育改革分析。教育資料與研究雙月刊,68,221-240。
7. 04.江永哲、黃隆明,1990, “防風網最佳間距配置之研究” ,農林學報39(2),
8. 04.江永哲、黃隆明,1990, “防風網最佳間距配置之研究” ,農林學報39(2),
9. 康淑雲(2004)。臺灣地區幼兒家長行使教育選擇的可能問題與省思。國民教育,44(3),39-46。
10. 康淑雲(2004)。臺灣地區幼兒家長行使教育選擇的可能問題與省思。國民教育,44(3),39-46。
11. 紀紈紳(2001)。感覺真好─教育的行銷藝術。蒙特梭利雙月刊,36,26-30。
12. 紀紈紳(2001)。感覺真好─教育的行銷藝術。蒙特梭利雙月刊,36,26-30。
13. 林水順、莊英慎(2000)。技職學院行銷作為與特性認知分析-以國立勤益技術學院為例。中華管理學報,1(1),33-54。
14. 林水順、莊英慎(2000)。技職學院行銷作為與特性認知分析-以國立勤益技術學院為例。中華管理學報,1(1),33-54。
15. 沈姍姍(1998)。自家長教育選擇權看教育機會均等。教育資料與研究雙月刊,21,8-10。