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系統識別號 U0026-0812200911421650
論文名稱(中文) 溶菌酵素、褪黑激素及雌性素對酒精引起的 胃部氧化及出血性潰瘍的保護作用
論文名稱(英文) Protective Effects of Several Drugs on Ethanol-induced Gastric Oxidative Stress and Hemorrhagic Ulcer in Rats
校院名稱 成功大學
系所名稱(中) 藥理學研究所
系所名稱(英) Department of Pharmacology
學年度 93
學期 2
出版年 94
研究生(中文) 林容瑩
研究生(英文) Rung-Ying Lin
電子信箱 fairyla21@yahoo.com.tw
學號 s2692112
學位類別 碩士
語文別 中文
論文頁數 82頁
口試委員 指導教授-洪正路
口試委員-王錫崗
口試委員-蔡麗雪
中文關鍵字 胃潰瘍  溶菌酵素  酒精潰瘍  雌性素  胃黏膜  褪黑激素 
英文關鍵字 ethanol-induced ulcer  lysozyme  gastric mucosa  estrogens  melatonin  gastric hemorrhagic ulcer 
學科別分類
中文摘要   在生物體中自然存在一些物質,如:人體很多組織中有表現的抗菌物質-溶菌酵素(lysozyme)已經發現具有很多藥理作用可緩解疾病;而松果腺所分泌的褪黑激素(melatonin)除了調控生理時鐘也有自由基清除效果;調控女性生殖的雌性素(estrogens)等,這些影響免疫、神經或調控生殖系統的酵素或激素對胃黏膜有無保護作用仍是未知,我們以會引起黏膜傷害和胃炎的酒精作為研究胃潰瘍模式,而上述物質的療效或作用機轉如何?尚未有充分明確的動物實驗作依據。本實驗即探討:lysozyme, melatonin 和estrogen 是否對酒精引起胃潰瘍有保護作用。

  實驗動物使用Wistar 品系的公老鼠,在約260-320 克重時絕食24小時後施行胃部手術,接著以酸化酒精(20﹪乙醇的生理酸溶液)灌流入胃腔作用3 小時。在酒精潰瘍組,我們觀察到嚴重的出血潰瘍、胃酸逆擴散增加、脂質過氧化物(LPO)生成、麩胺基硫(GSH)被消耗、胃血流降低(作用20 分鐘後)及黏液含量降低等。

  從給藥組實驗結果中觀察到腹膜內注射溶菌酵素劑量相關的抑制了潰瘍參數的惡化,而indomethacin 5 mg/kg 拮抗了溶菌酵素和褪黑激素的保護作用,褪黑激素在氧化自由基相關的參數(增加GSH 和減少LPO生成)有最好的正面影響;雌性素也呈現很好的改善結果,但是在酸逆流和胃出血的指標上不明顯,此外,我們也發現到雌性素使胃黏膜增厚和血流增加(給藥後5 到20 分鐘)的情形。而indomethacin 意料外的改善酒精造成的傷害,此抗發炎藥物可能因抗發炎機轉,減少胃出血和組織胺釋出,抵制酒精潰瘍形成。

  總結以上,這些生物體中自然合成的物質可以強化胃黏膜防禦力,且它們的保護作用包含了不盡相同的機轉。溶菌酵素可能是因具有抗氧化作用、增加PGE2 含量以及黏膜修復能力,使酒精潰瘍被抑制;褪黑激素藉由增加保護性的GSH、PGE2、黏液合成和優異的自由基清除能力而保護胃黏膜;雌性素主要是透過增加胃血流而強化胃黏膜對酒精的抵抗力。
英文摘要   Some compounds primarily have effects on immune, neural or even reproductive systems naturally occurring or synthetic in organisms and their effects on gastric damage are unknown. For instance: Lysozyme chloride possesses multiple pharmacological actions on various diseases. Melatonin has been well known as a free-radical scavenger. Estrogens play an important role in reproductive physiology. However, their actions on gastric mucosal protection have not yet been extensively studied. The aim was to study their effects on gastric oxidative stress and hemorrhagic ulcer in ethanol-treated rats.

  Male Wistar rats weighing 260-320 g were deprived of food for 24 h followed by gastric surgical procedure. After gastric surgery, rat stomachs were irrigated for 3 h with acidified ethanol(20% ethanol in gastric juice ) or gastric juice. Drugs were challenged either intragastrically or intraperitoneally 30 min before acidified ethanol-irrigation. Aggravation of gastric acid back-diffusion, mucosal lipid peroxide generation and hemorrhagic ulcer as well as attenuation of mucosal glutathione levels, mucus production and blood flow(20 min later after ethanol administration ) was achieved in acidified ethanol-treated rats.
 
  Lysozyme chloride inhibited these ulcerogenic parameters dose-dependently. Its effect on these offensive and defensive parameters was reversed by indomethacin. Melotonin, which has the most significant influences on enhancing the levels of glutathione and suppressing the generation of lipid peroxides, also reduced ulcer formation. Otherwise, the edema of gastric wall was occurred in the group treated with estrogen (β-estradiol). Different time points, pretreatment or after surgery, of estrogen administration led to the diverse results. Pretreatment of estrogen suppressed most ulcerogenic parameters, except for the extent of acid-back diffusion and hemoglobin concentrations. Furthermore, an enhancement in mucosal blood flow was obtained 5 to 20 minutes after estrogen had been administered. Unexpectedly, indomethacin treatment released rat stomachs from ethanol attack. The depression of hemoglobin, histamine and mucus levels was observed in the administration of this anti-inflammatory drug .

  In conclusion, these drugs improve ethanol-induce hemorrahagic ulcer through distinct mechanisms. Lysozyme chloride-ameliorated gastric hemorrhagic ulcer is through its antioxidant and prostaglandin stimulating effect. Melatonin protects against ulceration by stimulating mucosal glutathione, PGE2 biosynthesis, mucus production and scavenging oxyradicals. Estrogen exerts gastroprotection via enhancing the mucosal blood flow.
論文目次 中文摘要……………………………………………………………… 1
英文摘要……………………………………………………………… 4

主文
壹、緒論……………………………………………………………… 7
貳、實驗方法與材料…………………………………………………21
参、結果………………………………………………………………32
肆、討論………………………………………………………………40
伍、結論………………………………………………………………49
參考文獻………………………………………………………………51
圖表及附錄……………………………………………………………59
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