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研究生:蔡金川
研究生(外文):Tsai, Chin-Chuan
論文名稱:中醫四方劑對實驗性肝損傷療效評估與抗氧化活性之關係探討
論文名稱(外文):Evalution of four perscsiptions of traditional Chinese medicine on experimental liver damage and study of the relationship between tepato-protective and antioxidant activity of them.
指導教授:林昭庚林昭庚引用關係高尚德高尚德引用關係許朝添許朝添引用關係
學位類別:博士
校院名稱:中國醫藥學院
系所名稱:中國醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:1997
畢業學年度:85
語文別:中文
論文頁數:136
中文關鍵詞:中醫四方劑抗氧化自由基四氯化碳半乳糖氨α-奈異硫氰酸酯
外文關鍵詞:four prescriptions of traditional Chinese medicineanti-oxidationfree radicalcarbon tetrachloride (CCl4)D-galactosamine (D-GalN)α-naphthylisothiocyanate (ANIT)
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Copyright (c) 1990, Microsoft Corp 肝病是國人常見的疾病。從事傳統醫藥研究評估與作用機轉之探討,將有助於中醫藥對肝病防治之提升,增進國人健康,對於繼承和發揚傳統醫藥有深遠意義。本計畫擬以臨床著效四個方劑:桂枝茯苓丸、四磨飲、瀉青丸和四逆散之水抽出物進行研究。首先,以四氯化碳(CCl4)誘發大白鼠急性肝損傷,進行保肝效果之確定、再而模擬臨床運用(針對預防、治療)以及多重暴露毒物等之療效評估,包括:生化檢測、組織病理觀察。
另外對老鼠肝臟均質漿作脂質過氧化之藥理學研究,並且對組織內主要抗氧化酵素(SOD、Catalase、GSH-Px)進行機轉探討。其次,進行其它相關肝損傷模型之療效探討包括:(1):半乳糖氨(D-galactosamine):代謝競爭性損傷、生化指標和病理變化類似病毒性肝炎;(2)α-奈異硫氰酸酯(α-Naphthylisothiocyanate):膽汁鬱積性黃疸,高膽紅素血症等肝毒性物質誘發不同肝損傷,以期對治療肝病之中醫藥作深入之探討。
實驗結果顯示:(1)半乳糖氨致毒模型中,以桂枝茯苓丸療效最好。(2) α-奈異硫氰酸酯致毒模型中:預防以四磨飲效果最好,瀉青丸效果較差;治療以四逆散效果最好,桂枝茯苓丸效果較差,瀉青丸有利膽作用,而肝細胞之保護功能較少。(3)四氯化碳致毒模型中,四個方劑皆有顯著保肝作用。在單劑誘毒中,預防以四逆散效果最好;治療以四磨飲效果最好;在多重暴露毒物模型中以瀉青丸效果最佳。而且此四種方劑確具抑制脂質過氧化作用、保護抗氧化酵素Catalase之活性、抑制SOD之代償作用。
經此現代科學分析與考驗,證實此四個方劑所具抗氧化、消除自由基之能力在其防治機制中扮演重要角色。
As an endemic area of liver disease in China, the hazard, including chronic hepatitis and cirrhosis, became one of the Ten Leading Cause of Death in Taiwan Area for years. Traditional Chinese medicine (TCM) proved to be useful in the remedy of liver trouble. Interest in TCM on hepatic medications has increased wildly in recent years. If more scientific information on the mechanisms of TCM became available, more effective TCM in promotion and ministering the health of people would be possible. Along these lines, studies have been done in this issue. Liver damages induced by D-galactosamine (D-GalN), a- naphthylisothiocyanate (ANIT) and carbon tetrachloride (CCl4) in rats were conducted to elucidate the hepatoprotective effects of TCM and study the essence of it. Water extracts of four prescriptions of TCM: Syh-Mo-Yiin (SMY), Guizhi-Fuling Wan (GFW), Shieh-Qing-Wan (SQW) and Syh-Nih-Sann (SNS), concerning the use in the remedy of liver trouble in various types, were used in this study.
To examine the pharmacological activities of these recipes, the following experimental models were employed, first these extracts were administrated intraperitoneally in model of single dosing by D-GalN and CCl4, then pre- and post-treatment orally in model of ANIT and CCl4 intoxication, thus demonstrating their effect as a prophylactic and curative, in the last these four recipes had been assessed against multiple CCl4 insult in rats.
The protective action against D-GalN toxicity is of clinical importance because there is a close resemblance between the multifocal necrosis produced by D-GalN and the lesion of viral hepatitis in human.
Treatments by all the four extracts significantly reduced the damages provoked by D-GalN, and the affect of GFW was the most potent. The administration of ANIT to rats produces hyperbilirubinemia and cholestasis. These effects have led to the use of ANIT as an experimental tool for elucidating the mechanism of chemically induced cholestasis. In model of pre-treatment, SMY was the most potent and SQW had few effect statistically. In post-treatment all the recipes significantly reduced the damage by ANIT- intoxication, except the GFW. The SNS showed the most poten of them, SQW showed possessing some choleretic effect without any hepatocellular protective effect. CCl4, a well established and extensively used hepatotoxin, belong to a class of radical- generating xenobiotics, induced cellular necrosis by the free radicals CCl3.and CCl3OO.attack methylene carbons of polyenoic fatty acid of the membrane phospholipids, thus initiating onset of lipid peroxidation. In model of pre-treatment, SNS was the most potent. In case of curative, SMY was the most potent. SQW showed the most poten hepatoprotective effect in CCl4 repeated exposures. Treatment with these four exyracts caused a decrease in the elevated peroxidative levels. In oxidative stress, SOD activity in the liver of CCl4-intoxicated rats was increased compensatively. Treatment showed a decrease in the enzyme activity except the extract of GFW. The disturbance of enzyme, catalase, by CCl4 insulting was corrected.
The results showed that the four recipes mentioned above did possess hepato-protective activity and they also exhibited antioxidant effect in lipid peroxidation inhibitory activity and antagonized with CCl4-insult in the disturbances of antioxidant enzymes. It suggested that the activity of free radical scavenging and antioxidant of them could play one part in their hepatoprotective effects.
封面
目錄
論文摘要
第一章 前言
第二章 文獻探討
第一節 黃疸的考據
第二節 脅痛的考據
第三節 瘀血的考據
第四節 癥積的考據
第五節 臌脹的考據
第六節 現代醫學概述
第七節 綜結
第三章 材料與方法
第一部分 實驗前準備及實驗大綱
第一節 藥品與器材
第二節 方劑藥材之準備
第三節 方劑水抽出物之製備
第四節 實驗動物
第五節 統計學分析
第二部分 實驗研究
『甲』方劑療效之確定(腹腔注射投與)
第一節 實驗ID-半乳糖氨(D-GalN)誘發大白鼠急性肝細胞毒性試驗
第二節 實驗II四氯化碳(CC14)誘發大白鼠急性肝細胞毒性試驗
『乙』方劑療效之評估(經口胃管投與)
第三節 實驗III奈異硫氰酸酯(ANIT)誘發大白鼠膽道瘀阻─事先投與─預防評估
第四節 實驗IV奈異硫氰酸酯(ANIT)誘發大白鼠膽道瘀阻─事先投與─治療評估
第五節 實驗V四氯化碳(CC14)誘發大白鼠急性肝細胞毒性─事先投與─預防評估
第六節 實驗VI四氯化碳(CC14)誘發大白鼠急性肝細胞毒性─事先投與─治療評估
『丙』模擬環境多重暴露之療效評估與作用機轉探討
第七節 實驗VII四氯化碳(CC14)多重暴露誘發肝毒性之療效評估
作用機轉探討:脂質過氧化(LPO)之檢量
作用機轉探討:抗氧化酵素之檢量
(1)SOD
(2)CAT
(3)GSH-Px
第四章 結果
『甲』方劑療效之確定(腹腔注射投與)
第一節 實驗ID-半乳糖氨(D-GalN)誘發大白鼠急性肝細胞毒性試驗
第二節 實驗II四氯化碳(CC14)誘發大白鼠急性肝細胞毒性試驗
『乙』方劑療效之評估(經口胃管投與)
第三節 實驗III奈異硫氰酸酯(ANIT)誘發大白鼠膽道瘀阻─事先投與─預防評估
第四節 實驗IV奈異硫氰酸酯(ANIT)誘發大白鼠膽道瘀阻─事先投與─治療評估
第五節 實驗V四氯化碳(CC14)誘發大白鼠急性肝細胞毒性─事先投與─預防評估
第六節 實驗VI四氯化碳(CC14)誘發大白鼠急性肝細胞毒性─事先投與─治療評估
『丙』模擬環境多重暴露之療效評估與作用機轉探討
第七節 實驗VII四氯化碳(CC14)多重暴露誘發肝毒性之療效評估
作用機轉探討
第五章 討論
第六章 結論
參考文獻
附錄(研究成果)
謝辭
英文摘要
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