跳到主要內容

臺灣博碩士論文加值系統

(216.73.216.23) 您好!臺灣時間:2025/10/27 08:49
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

我願授權國圖
: 
twitterline
研究生:楊博仁
研究生(外文):Po-Jen Yang
論文名稱:以動物模式評估板藍根對肺纖維化防治的影響
論文名稱(外文):The effect of Isatis indigotica radix extract in experimental murine model of pulmonary fibrosis
指導教授:張永勳張永勳引用關係
學位類別:碩士
校院名稱:中國醫藥大學
系所名稱:中國藥學研究所碩士班
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2007
畢業學年度:96
語文別:中文
論文頁數:90
中文關鍵詞:肺纖維化
外文關鍵詞:fibrosisbleomycin
相關次數:
  • 被引用被引用:1
  • 點閱點閱:425
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
板藍根的基原為十字花科菘藍Isatis indigotica FORTUNE的乾燥根,為一種清熱解毒、涼血利咽的中藥材,對於流感、腮腺炎、肝炎、喉痹咽腫等症狀皆有療效。SARS期間,板藍根是幾種台灣常用的藥材之一,由中醫理論可以得知SARS屬於溫疫的範疇,其表徵為高熱、惡寒、全身痠痛、咳嗽、喉嚨炎等症狀,癒後會衍生肺炎及肺纖維化。本研究利用清熱解毒的中藥材板藍根,以動物模型來評估板藍根對肺纖維化防治的效果。
本研究經由全自動生化分析儀以及分光光度計來分析投予不同劑量的板藍根甲醇粗抽物下,經由bleomycin誘導肺部急性發炎及慢性纖維化期間,其肺臟組織內生化值的變化情形。實驗結果發現,在急性發炎期間,菘藍甲醇粗抽物對肺臟的抗氧化酵素穀胱苷肽還原酶(Glutathione reductase,GR)和超氧歧化酶(Superoxide dismutase,SOD)的活性有向上提升的作用並會減少肺臟組織中腫瘤壞死因子(Tumor Necrosis Factor-α,TNF-α)及肺臟組織中白介素-1β(Interleukin-1β,IL-1β)。經過動物模型誘導的肺臟發炎,持續的投予板藍根甲醇粗抽物能夠有效提升肺臟抗氧化酵素的活性,而且發現在高劑量(1.0 g/kg)下有顯著的效果。經由肺臟檢體的組織切片染色後,可以用半定量型態學分析來判斷肺臟的發炎情形;經過判讀後,結果和測定出來的生化值有相同的趨勢,在投予板藍根甲醇粗抽物後,減輕了肺臟的發炎程度。另一方面,經過七週持續投予板藍根甲醇粗抽物後,透過肺臟組織hydroxyproline的定量,膠原蛋白的測定,TGF-β的含量與纖維化組織特殊染色來了解板藍根對於纖維化防治的影響。測定結果顯示,高劑量(1.0 g/kg)的菘藍甲醇粗抽物能夠有效降低肺臟組織水解脯氨酸、膠原蛋白、TGF-β的濃度。
由此可知,高劑量(1.0 g/kg)的菘藍甲醇粗抽物能夠有效降低肺臟經過bleomycin的氧化傷害,更進ㄧ步降低纖維母細胞分泌的膠原蛋白含量,減低肺部纖維化的程度。
The root of Isatis indigotica FORTUNE (Cruciferae), popularly known as Ban-Lan-Gen, was used in traditional Chinese medicine for seasonal febrile diseases, mumps, hepatitis, inflammatory diseases, and sore throat.

During the SARS epidemic in 2003 in Taiwan, Ban-Lan-Gan was one of the most commonly used Chinese herb. In traditional Chinese medical science, SARS was one kind of pestilence with several severe syndromes, such as high fevers, chills, aches, coughs and faucitis. SARS was accounted for pneumonia and pulmonary fibrosis in the later stage. In this study, we evaluated the effect of Isatis indigotica radix extract in experimental murine model against pulmonary fibrosis.

In this study, the effects of different doses of methanol extracts of Isatis indigotica radix (II-RMeOH) on pulmonary fibrosis induced by intranasal inoculated bleomycin for 3 weeks in C57BL/6J mice were assayed by a spectrophotometer and a clinical chemistry analyzer. The results showed that II-RMeOH (1.0 g/ kg) caused significant increase in superoxide dismutase (SOD) and glutathione reducetase (GR) activeities; moreover, it also caused critical decrease in tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) level in mouse lung tissue.

Hematoxylin/ eosin staining indicated the inflammatory lung injury and the degree of inflammation by semiquantitative morphological index (SMI). On the other hand, after 7-week gavaging abidingly, the effect of II-RMeOH on the bleomycin-induced chronic pulmonary fibrosis was investigated. The study was evaluated by measuring the hydroxylproline, collagen, transforming growth factor-β1 (TGF-β1), and microwave Masson’s trichrome stain. The result showed that high-dose II-RMeOH (1.0 g/ kg) could significantly lower the contents of hydroxylproline, collagen, and TGF-β1 in lung tissue. Therefore, high-dose II-RMeOH (1.0 g/ kg) could reduce the bleomycin-induced lung inflammation. More over, it could diminish the collagen secretion by fibroblast and decrease the degree of pulmonary fibrosis.
目錄Ⅰ
略字表Ⅲ
圖目錄Ⅳ
摘要Ⅵ
英文摘要Ⅷ
第一章 緒 言1
第二章 總 論3
第一節 菘藍的文獻考察3
一、 板藍根的本草學考察3
二、 菘藍的藥用植物學考察10
三、 菘藍的成分文獻考察12
四、 菘藍的藥理作用文獻考察13
第二節 肺纖維化的形成16
一、 肺纖維化形成的機轉16
二、 氧化壓力和肺臟疾病19
三、 肺纖維化實驗動物模型和其原理21
第三節 自由基產生的氧化性損傷與發炎的關係23
ㄧ、發炎與過氧化的關聯性23
二、自由基的種類和特性25
三、抗氧化和自由基的關聯28
第三章 實驗材料與方法30
第一節 實驗材料30
一、 材料的製備30
二、 試藥30
三、 實驗儀器31
四、 實驗動物 32
第二節 實驗方法33
一、 抗發炎實驗模式33
二、 防治肺纖維化實驗模式42
第三節 統計分析45
第四章 實驗結果46
一、 肺纖維化前期抗發炎實驗46
二、 菘藍防治肺纖維化實驗64
第五章 討論69
第六章 結論75
參考文獻 81
. 國家藥典委員會,中華人民共和國藥典二○○○年版一部,化學工業出版社,北京 2000;pp. 163-164。
. 林宜信主編:台灣中醫藥防治SARS關鍵成果彙編(一),行政院衛生署中醫藥委員會出版,台北,2004;pp. 2-5, pp. 86-95, PP. 196-201。
. 李鳴真,葉望云,陶付耳:清熱解毒法實質的研究,浙江中西醫結合雜誌2000;10(8) :449。
. 明•李時珍:本草綱目,國立中國醫藥研究所,台北 1976;pp. 126-128, p. 572, pp. 634-637。
. 國家中醫藥管理局《中華本草》編委會:中華本草(全十冊),上海科學技術出版社,上海,1999; Vol 3 pp. 709-715 。
. 中國醫學科學院藥物研究所等編: 中藥志第一冊,人民衛生出版社,北京1993; pp.453-458。
. 梁•陶弘景,尚志鈞輯校:名醫別錄(校輯本),人民衛生出版社,北京1986;p. 55。
. 那琦、謝文全:重輯名醫別錄卷1,中國醫藥學院中國藥學研究所,台中1977;P. 38。
. 梁•陶弘景校注、小島尚真、森立之重輯、岡西為人訂補解題:本草經集注卷三,南大阪印刷株式會社,大阪,1972;p. 44。
.岡西為人重輯:重輯新修本草,國立中國醫藥研究所,台北 1982;p. 179, p. 203。
.尚志鈞:開寶本草輯復本,安徽科學技術出版社,合肥1998;P. 171, P. 188, P. 215。
.宋•唐慎微撰、艾晟校定、吳家鏡譯述:經史證類大觀本草,正言出版社,台南1977;pp. 176-177, p. 239。
.宋•唐慎微原著、金•張存惠重刊、那琦解題並序、魏德文索引刊行:重修政和經史備用本草卷7,南天書局,台北1976;pp.172-173。
.清•吳其濬:植物名實圖考長編,世界書局,台北1974;pp. 422-47, p. 511。
.清•吳其濬:植物名實圖考,世界書局,台北1974;pp. 259-261, p.293。
.黃康泰、丁志遵、趙守訓、嚴永清、徐國鈞、陳廉、余傳隆、高宣亮、張智德主編,現代本草綱目上卷,中國醫藥科技出版社,北京,2001年;p. 1516。
.何玉鈴:板藍根、大青葉及青黛之生藥學及藥理學研究,中國醫藥大學中國藥學研究所博士論文,台中,2001;pp. 8-26。
.黃增泉著、國立編譯館主編:植物分類學,南天書局,台北,1993;pp. 190~194 。
.鄧伯林:青黛中靛藍與靛玉紅直接比色測定法,中草藥1986; 17 (4): 163-164。
.鄧伯林:柱層層析分光光度法測定中藥青黛中靛藍與靛玉紅含量,中草藥1981; 12 (6): 11-15。
.張時行:靛青根化學成分的研究,中草藥1983; 14 (6): 6-8。
.陳發奎、陳克梅、郭允珍:菘藍葉中靛玉紅的提取與分離,瀋陽醫學院學報1986; 3(3): 194。
.梁文法、畢業範、陳通、廬華、陳勇、甄漢深:層掃描法測定菘藍根和葉中靛玉紅與靛藍的含量,中草藥1990; 21(4): 11-12。
.Wu XY, Liu YH, Sheng WY, Sun J, Qin GW: Chemical constituents of Isatis indigotica. Planta Med 1997; 63 (1): 55-57.
.Huang QS, Yoshihira K, Natori S: Isolation of 2-hydroxy-3-butenyl thiocyanate, epigotrin and adenosine from ''Banlangen'', Isatis indigotica root. Planta Med 1981; 42: 308-310.
.Gilbert KG, Hill DJ, Crespo C, Mas A, Lewis M, Rudolph B, Cooke DT: Qualitative analysis of indigo precursors by HPLC and HPLC-MS. Phytochem Anal 2000; 11 (1): 18-20.
.Wu XY, Qin GW, Cheung KK, Cheng KF: New alkaloids from Isatis indigotica. Tetrahedron 1997; 53 (39): 13323-13328.
.Deng KM, Wu XY, Yang GJ, Qin GW: Alkaloids from Isatis indigotica. Chin Chem Lett 1997; 8 (3): 237-238.
.黃喬書:板藍根化學成分的研究,藥學學報1981; 16 (3): 182-183。
.郭景周:板藍根液沖洗淚道治療急慢性類囊炎100例,中醫雜誌1987; 3: 216。
.劉雲海、李清香、石玉梅:大青葉抗內毒素試驗,中藥材1994; 17(6):36-37。
.Hesbert A, Bottin MC, De Ceaurriz J, Protois JC, Cavelier C: Testing natural indigo for genotoxicity. Toxicol Lett 1984; 211:119-125
.歐明、林勵、李衍文:簡明中藥成份手冊,中國醫藥科技出版社 2003; p. 217。
.籍秀娟、張福榮:合成靛玉紅的抗腫瘤作用及毒性研究,藥學學報 1981; 16:146-147。
.吳冠芸、方福德、劉敬忠、張安、侯虞華:靛玉紅治療慢性粒細胞白血病療效原理的研究-I.對人外周血白血病細胞DNA、RNA和蛋白質合成的影響,中華醫學雜誌 1980; 60(8): 451-454。
.吳冠芸、劉敬忠、方福德、左瑾:靛玉紅治療慢性粒細胞白血病療效原理的研究-靛玉紅與DNA的結作用及其結合鍵合型的鑒別,中國科學(B輯)1982; 5: 436-443。
.籍秀娟、張福榮:靛玉紅類化合物的抗腫瘤作用及結構活性關係的研究,藥學學報 1985; 20: 137-139。
.靛玉紅臨床治療協作組:靛玉紅治療314例慢性粒細胞白血病的臨床研究,中華血液雜誌 1980; 1:132。
.張鐳、吳冠芸、邱長春、高百紅:靛玉紅治療慢性粒細胞白血病療效原理的研究-VI.靛玉紅對無細胞體系DNA合成的抑制作用,中國醫學科學院學報 1985; 7(2): 112-115。
.Toshio Kunikata, Tomoki Tatefuji, Hajime Aga, Kanso Iwaki, Masao Ikeda and Masashi Kurimoto. Indirubin inhibits inflammatory reactions in delayed-type hypersensitivity. Eur J Pharmaco2000; 410:93-100
. Clark JG, Overton JE, Marino BA, Uitto J and Starcher BC. Collagen biosynthesis in bleomyc-induced pulmonary fibrosis in hamsters. J Lab Clim Med 1980; 96:943-953
.Selman, M., M. Montano, C. Ramos, R. Barrios, and R. Perez-Tamayo. Experimental pulmonary ifbrosis induced by paraquat plus oxygen in rats: a morphologic and biochemical sequential study. Exp. Mol. Pathol.1989; 50:147-166
.Wang, Q. J., S. N. Giri, D. M. Hyde, and C. Li. Amelioration of belomycin-induced pulmonary fibrosis in hamsters by combined treatment with taruine and miacin. Biochem. Pharmacol. 1991; 42:1115-1122
.Francois Huaux, Mohammed Arras, David Tomasi, Virginie Barbarin, and Dominique. Lison.IL-12p40 and experimental lung fibrosis. The Journal of Immunolony.2002:2653-2661
. Seyer JM, Hutcheson ET and Kang AH. Collagen polymorphism in idiopathic chronic pulmonary fibrosis. J Clin Invest 1976; 57:1498-1507
.Daniels CE, Wilke MC, Edens M, Kottom TJ, Murphy SJ, Limper AH, Leof EB. Imatinib mysylate inhibits the profibrogenic activity of TGF-beta and prevents bleomycin-mediated lung fibrosis. J Clin Invest 2004; 114:1308-1316
.Barber DA, Harris SR. Oxygen free radicals and antioxidant: a review. Am Pharm 1994; 34(9):26-35
.Moskovitz J, Yim MB, Chock P B. Free radicals and disease. Arch Biochem Biophys 2002; 397:354-359
.Ward Pa, Hunninghake GW. Lung inflammation and fibrosis. Am J Respir Crit Care Med 1998; 157:123-129
.Rahman I, Skwarska E, Henry M, Davis M, O’Connor CM, FitzGeraldMX, Greening A, MacNee W. Systemic and pulmonary oxidative stress in idiopathic pulmonary Fibrosis. Free Radic Biol Med 1999; 27:60-68
.G. Izbicki, M. J. Segel, and R. Breuer. Time course of bleomycin-induced lung fibrosis. Int. J. Exp. Path. (2002) 83, 111-119
.蔡坤道:三七治療小鼠肺纖維化之應用評估,中國醫藥大學中西醫結合研究所,台中,2004;p. 7。
.Cheruyl L. Fattman, Ling-Yi Chang,Toni A. Termin, and Tim D. Oury. Enhanced bleomycin-induced pulmonary damage in mice lacking extracellular superoxide dismutase. Free Radic Biol Med, 2003; 35:763-771
.黃信維:倒地蜈蚣及其活性成分betulin 鎮痛及抗發炎作用機轉之研究,中國醫藥大學中國藥學研究所碩士論文,台中,2006;P. 20。
.Bokov A, Chaudhuri A, Richardson A. The role of oxidative damage and stress in aging. Mech Aging Dev 2004;125:811-826
.Guix FX, Uribesalgo I, Coma M, Munoz FJ. The physiology and pathophysiology of nitric oxide in the brain. Prog Neurobiol 2005; 76:126-52
.陳瑗、周玫主編:自由基與衰老,人民衛生出版社,北京,2004;pp. 8-9。
Sausville EA, Peisach J, Horwitz SB. Effect of chelating agents and metal ions on the degradation of DNA by bleomycin. Biochem 1978; 17:2740-2746
.Sausville EA, Stein RW, Peisach J, and Horwitz SB. Properties and products of the degradation of DNA by bleomycin and iron. Biochemistry1978; 17:2746-2754
.Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 2006; 160(1):1-40
.McCord JM, Fridovich I. Superoxide dismutase. An enzymic function forerythrocuprein hemocuprein. J Biol Chem. 1969;244:6049-6055.
.Man Pyo Chung, Martha M. Monick, Nabeel Y. Hamzeh, Noah S. Butler, Linda S. Powers, and Gary W. Hunninghake. Role of repeatedlung injury and genetic background in bleomycin-induced fibrosis. Am J Respir Cell Mol Biol2003; 29:375-380.
.Brown, R. F., R. B. Drawbaugh, and T. C. Marrs. An investigation of possible models for the production of progressive pulmonary fibrosis in the rat: the effects of repeated intratracheal instillation of bleomycin. Toxicology 1988; 51:101-110
.洪熒駿:車前草及其活性成分熊果酸鎮痛及抗發炎作用機轉之研究,中國醫藥大學中國藥學研究所碩士論文,台中,2006;p. 26。
.Kraus RJ, Ganther HE. Reaction of cyanide with glutathione peroxidase. Biochem Biophys Res Commun. 1980; 19:1116-1122
.Prohaska JR, Oh SH, Hoekstra WG, Ganther HE. Glutathione peroxidase: inhibition by cyanide and release of selenium. Biochem Biophys Res Commun. 1977; 74:64-71
.Woolliams JA, Wiener G, Anderson PH, McMurray CH. Variation in the activities of glutathione peroxidase and superoxide dismutase and in the concentration of copper in the blood in various breed crosses of sheep. Res Vet Sci. 1983; 34:253-256
.Anderson ME. Punchard NA, Kelly FJ. Free Radicals: A Practical Approach. New York: Oxford University Press. 1996; 213-226
.Guntherberg H, Rost J. The true oxidized glutathione content of red blood cells obtained by new enzymic and paper chromatographic methods. Anal Biochem. 1966; 15:205-210
.Ataoglu T, Ungor M, Serpek B, Haliloglu S, Ataoglu H, Ari H. Interleukin-1 beta and tumour necrosis factor-alpha levels in periapical exudates. Int Endod J. 2002; 35:181
.Kremer S., Breuer R., Lossos I.S. ET AL. Effect of immunomodulators on bleomycin-induced lung injury. Respiration 1999; 66:455-462
.Ward PA, Hunninghake GW. Lung inflammation and fibrosis. Am J Respir Crit Care Med 1998; 157:S123-129
. Martin Kolb, Peter J. Margetts, Patricia J. Sime, and Jack Gauldie. Proteoglycans decorin and biglycan differentially modulate TGF-β-mediated fibrotic responses in the lung. Am J Physiol Lung Cell Mol Physiol. 2001; 280:1327-1334
. Reiser KM, Tryka AF, Lindenschmidt RC, Last JA and Wistschi JP. Changes in collagen cross-linking in bleomycin-induced pulmonary fibrosis. J Biochem Toxicol 1986; 83:83-91
.Nveed I. Chaudhary, Andreas Schnapp, and John E. Park. Pharmacologic differentiation of inflammation and fibrosis in the rat bleomycin model. Am J Respir Criti Care Med 2006; 173:769-776
.Crooke ST and Branter WT. Bleomycin, a review J Med 1976; 7:333-427
. Mohamed H. Daba, Abdel-Aziz H. Abdel-Aziz, Adel M. Moustafa, and Hassan A. El-Kashef. Effects of L-carnitine and Ginkgo biloba extract (EGb 761) in experimental bleomycin-induced lung fibrosis. Pharmacol Res 2002; 45:461-467
.Boris Manoury, Soizig Nenan, Isabelle Guenon, Vincent Lagente, Elisabeth Bosichot. Influence of early neutrophil depletion in MMPs/TIMP-1 balance in bleomycin-induced lung fibrosis. Int Immunopharmacol 2007; 7:900-911
.Huseyin Ozyurt, Sadik Sogut, Zeki Yildirim, and Omer Akyol. Inhibitory effect of caffeic acid phenethy ester on bleomycine-induced lung fibrosis in rats. Clin Chim Acta 2004; 339:65-75
Zeki Yildirim, Mahir Kotuk, Mustafa Iraz, and Suleyman Ozen. Attenuation of bleomycin-induced lung fibrosis by oral sulfhydryl containing antioxidants in rats: endosteine and N-acetylcysteine. Pulm Pharmaco Ther 2005; 18:367-373
.Hu WH, Johnson H, Shu HB. Tumor necrosis factor-related apoptosis inducing ligand receptors signal NF-Κb and JNK activation and apoptosis through distinct pathway. J. Biol. Chem. 1999; 274:30603-30610
.Papiernik M, Homo-Delarche F. Thymic reticulum in mice. III. Phagocytic cells of the thymic reticulum in culture secrete both prostaglandin E2 and interleukin-1which regulate thymocyte proliferation. Eur J Immunol. 1983; 13:689-692
.Woessner Jr JF. The determination of hydroxyproline in tissue of bleomycin-induced pulmonary fibrosis in neutrophil-depleted and complement-depleted rats. Am J Pathol 1981; 93:440-447
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top