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研究生:林孟儀
研究生(外文):Lin, Mengyi
論文名稱:白花蛇舌草對乙醯胺酚誘發小鼠肝損傷之抗氧化及護肝作用
論文名稱(外文):Antioxidative and hepatoprotective effects of Hedyotis diffusa on acetaminophen-induced liver damage in mice
指導教授:盧義發盧義發引用關係
口試委員:沈立言江孟燦趙璧玉翁孟仕
口試日期:100/6/23
學位類別:碩士
校院名稱:輔仁大學
系所名稱:營養科學系
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
論文出版年:2011
畢業學年度:99
語文別:中文
論文頁數:87
中文關鍵詞:白花蛇舌草乙醯胺酚抗氧化肝損傷護肝作用
外文關鍵詞:Hedyotis diffusaacetaminophenantioxidantliver damagehepatoprotective effects
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乙醯胺酚 (N-acetyl-para-aminophenol, acetaminophen, APAP) 為常用之鎮熱解痛藥物成分,但過量服用會導致肝臟損傷。白花蛇舌草 (Hedyotis diffusa, HD) 是台灣民間的中草藥,亦常作為青草茶飲用,近年研究發現白花蛇舌草具有抗氧化、抗腫瘤及免疫調節等特性。本研究欲探討白花蛇舌草對APAP誘導小鼠肝損傷是否具有改善的效果。將白花蛇舌草以不同溶劑 (水、50 %酒精與95 %酒精) 萃取,以總抗氧化能力、DPPH自由基清除率、還原力及總多酚含量等為指標,挑選效果較佳之萃取方式,進行動物實驗。將60隻BALB/c小鼠隨機分成五組,並給予各組共四週管餵不同處理:分別為控制組、負控制組、正控制組 (N-acetylcysteine 600 mg/kg bw) 及不同劑量之白花蛇舌草組 (分別為300、900 mg/kg bw) 。除控制組外,第二週開始給予每週腹腔注射兩次APAP (400 mg/kg bw) 誘導肝損傷,實驗中每週進行一次採血,評估肝臟功能,實驗結束後將小鼠犧牲,取集血液及肝臟進行分析。結果顯示,白花蛇舌草以95 %及50 %乙醇萃取物有較佳的體外抗氧化能力。動物實驗中,經HD處理的組別 (300與900 mg/kg bw) 具有顯著降低血清中天門冬胺酸轉胺酶 (ALT) 和丙胺酸轉胺酶 (AST) 活性。此外,HD可增加麩胱甘肽硫轉移酶 (GST) 活性,並且提升麩胱甘肽 (GSH) 含量、GSH/GSSG比值及肝臟中總抗氧化能力(TEAC)。而高劑量HD (900 mg/kg bw) 明顯增加超氧歧化酶 (SOD) 與麩胱甘肽過氧化酶 (GPx) 活性。綜合結果,HD可提高抗氧化能力,達到減緩APAP所造成小鼠的肝損傷。
Acetaminophen (APAP) is a popular analgesic and antipyretic drug used at therapeutic doses. However, accidental or intentional ingestion of larger amounts causes severe hepatotoxicity. Hedyotis diffusa (HD) is a well-known Chinese folk medicine and also drunk as the herb tea. Recent researches had shown that it exhibits anti-inflammatory, anticarcinogenic and antioxidative activities. The present study was to investigate the antioxidative and hepatoprotective effect of HD against APAP-induced liver damage in BALB/c mice. The extracts of HD by various solvents (water, 50% ethanol, 95% ethanol) were used to compare the antioxidant activity in vitro, including trolox equivalent antioxidant capacity (TEAC), DPPH, reducing power and total phenolic contents, and to choose the best extracts to conduct animal study. The 60 male BALB/c mice were randomly divided into five groups and received the following treatments by gavage for four weeks: control group, negative control group, positive control group (N-acetylcysteine 600 mg/kg bw) and two HD groups at different dosages (300, 900 mg/kg bw, respectively). In addition, APAP (400 mg/kg bw) was administrated to the mice except those in the control group by intraperitoneal injection twice a week from the second week of experiment. Blood samples were collected once a week for measuring liver function. After animals sacrificed, collecting blood and the liver for further analyses. Our results showed that 95% and 50% ethanol extracts of HD had improved antioxidant capacity. In this animal study, mice treated with HD (300, 900 mg/kg bw) had significantly decreased levels of aspartate aminotransferase (ALT) and alanine aminotransferase (AST) compared with the negative control group. Moreover, HD could significantly increase glutathione S-transferase (GST) activity, as well as glutathione (GSH), GSH/GSSG and TEAC in liver. Nevertheless, high dose of HD significantly augment superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. Taken together, HD had protective effects against APAP-induced liver injury in mice through raising the antioxidant capacity.
頁次
中文摘要 ..................................................................................................... I
英文摘要 ..................................................................................................... II
致謝......................................................................................................... III
目錄 ........................................................................................................ IV
表目錄 ...................................................................................................... VII
圖目錄 ..................................................................................................... VIII
附圖目錄 ..................................................................................................... IX
壹、緒言 ......................................................................................................1
貳、文獻回顧 ...................................................................................................3
一、自由基與氧化壓力 ...........................................................................................3
(一) 自由基與活性氧 .........................................................................................3
(二) 自由基與活性氧來源 ......................................................................................3
(三) 氧化壓力與氧化傷害 ......................................................................................5
二、生物體內抗氧化及解毒系統 ....................................................................................6
(一) 抗氧化防禦系統 .........................................................................................6
(二) 解毒系統 ..............................................................................................7
三、肝臟 .....................................................................................................8
(一) 肝損傷定義 .............................................................................................9
(二) 肝損傷種類 ............................................................................................10
(三) 肝功能指標 ............................................................................................11
(四) 脂肪酸與肝損傷之關聯性...................................................................................12
四、乙醯胺酚 .................................................................................................13
(一) 乙醯胺酚之歷史背景 ......................................................................................13
(二) 乙醯胺酚之臨床應用 .....................................................................................14
(三) 乙醯胺酚之代謝與肝毒性 ..................................................................................15
(四) 乙醯胺酚之危險性及中毒劑量 ...............................................................................16
(五) 乙醯胺酚中毒之治療 .....................................................................................17
五、白花蛇舌草 ...............................................................................................18
(一) 白花蛇舌草的簡介 .......................................................................................18
(二) 白花蛇舌草的化學成分 ....................................................................................19
(三) 白花蛇舌草的生理活性 ....................................................................................19
(四) 白花蛇舌草的安全性 ......................................................................................20
参、材料與方法 ..................................................................................................22
一、目的 ....................................................................................................22
二、設計與架構 ...............................................................................................22
(一) 實驗I:不同溶劑萃取白花蛇舌草之體外抗氧化能力之比較 ..........................................................22
(二) 實驗II:白花蛇舌草萃取物對APAP誘導肝毒性之保護效果 ..........................................................23
三、材料 ....................................................................................................24
(一) 白花蛇舌草 ............................................................................................24
(二) 分析試藥 ..............................................................................................24
(三) 儀器設備 ..............................................................................................26
四、方法 ....................................................................................................27
實驗I:不同溶劑萃取白花蛇舌草之體外抗氧化能力之比較
(一) 樣品萃取 .............................................................................................27
(二) 樣品萃取物之抗氧化分析項目 ...............................................................................27
(三) 統計分析 .............................................................................................29
實驗II:白花蛇舌草萃取物對APAP誘導肝毒性之保護效果
(一) 動物品種..............................................................................................29
(二) 動物飼養條件與分組 .....................................................................................29
(三) 實驗設計 .............................................................................................30
(四) 樣品收集與處理 ........................................................................................30
(五) 樣品分析項目 ..........................................................................................31
(六) 統計分析 .............................................................................................36
肆、結果 ......................................................................................................37
一、實驗I 白花蛇舌草萃取物之體外抗氧化能力之比較 .................................................................. 37
(一) 白花蛇舌草之不同溶劑萃取物在清除 DPPH 自由基能力之比較 .......................................................37
(二) 白花蛇舌草之不同溶劑萃取物對還原力之比較 ...................................................................37
(三) 白花蛇舌草之不同溶劑萃取物對總多酚含量及總抗氧化能力之比較 .....................................................37
二、實驗II 白花蛇舌草萃取物對乙醯胺酚 (Acetaminophen, APAP) 誘發 BALB/c小鼠肝損傷之抗氧化及護肝作用 ....................38
(一) 體重、肝臟重量及肝臟對體重之相對重量之影響 ..................................................................38
(二) 血清肝功能指標之影響 ....................................................................................39
(三) 肝臟中抗氧化物質與肝臟解毒酵素之影響 .......................................................................40
(四) 肝臟中總抗氧化能力與脂質過氧化之影響 .......................................................................41
(五) 肝臟組織變化之影響 ......................................................................................41
(六) 肝臟脂肪酸組成之變化 ....................................................................................42
伍、討論 ......................................................................................................43
陸、結論 ......................................................................................................54
柒、參考文獻 ...................................................................................................66

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