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系統識別號 U0026-0812200914301860
論文名稱(中文) 雌激素對敗血症所誘發之胃炎的巨噬細胞移動抑制因子表現之影響
論文名稱(英文) Effect of estrogen on Macrophage Migration Inhibition Factor(MIF) in sepsis-induced gastritis
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 96
學期 2
出版年 97
研究生(中文) 簡澔宇
研究生(英文) Hao-Yu Jian
電子信箱 s2695101@mail.ncku.edu.tw
學號 S2695101
學位類別 碩士
語文別 中文
論文頁數 84頁
口試委員 口試委員-鄭瑞棠
口試委員-簡伯武
指導教授-洪正路
中文關鍵字 雌激素  光甘草定  敗血症  胃炎  巨噬細胞移動抑制因子 
英文關鍵字 gastritis  Estrogen  Macrophage Migration Inhibition Factor  MIF  Glabridin  sepsis 
學科別分類
中文摘要 巨噬細胞移動抑制因子(MIF)在敗血症、發炎、自體免疫疾病、免疫系統調控上扮演著重要角色,是一個近年來時常被研究探討的proinflammatory cytokine。近期研究指出,在胃炎(潰瘍)組織中可以發現到MIF有顯著性的增加,透過Anti-MIF 抗體阻斷MIF則能達到改善效果,因此MIF也是胃部病理過程的關鍵因子。嚴重敗血症會常伴隨多重器官衰竭,而LPS所誘導的敗血症動物模式會伴隨胃炎和潰瘍的產生,雖然過去研究鮮少探討敗血症與胃損傷的關係,但我們認為胃損傷是影響敗血症預後的重要因素。過去研究曾在其他胃潰瘍動物模型中發現女性荷爾蒙雌激素(Estrogen)具有保護作用,另外,Estrogen在一些組織的抗發炎作用也被廣為研究。因此本研究欲探討在敗血症誘導胃炎的模式中,Estrogen扮演何種角色,並探討是否會影響MIF表現,以及甘草黃酮Glabridin是否也有類似的作用?
結果顯示,LPS(10mg/kg)誘發敗血症10小時後大鼠胃部的MIF表現顯著提高,而其中經卵巢摘除(OVX)之大鼠的MIF表現更為上升,在合併投予Estradiol (0.5mg/kg)則能逆轉MIF的表現。然而我們也發現到MIF的表現和TNF-α、IL-1β、iNOS、NO的產生及組織的損傷程度呈現正相關,基於過去許多文獻報導,我們認為這有可能是MIF擴大了這些發炎因子的產生。另外我們也發現到Estradiol在此實驗模式下可增加GSH濃度,暗示著它可增加細胞抗氧化能力。而Glabridin (4mg/kg)在此實驗模式下有著與Estradiol類似的作用,且抑制發炎因子的能力略佳,其抗氧化的能力更顯著優於Estradiol。另外,我們也發現到Glabridin合併Tamoxifen的投予則能部份逆轉Glabridin的作用。
總結我們認為雌激素Estrogen及Glabridin在能在敗血症誘發胃炎的模式下扮演保護性的角色,除了強調雌激素的作用,更藉由對草本植物的探討,提供未來在開發敗血症相關之藥物、保健食品一個新方向。
英文摘要 Macrophage Migration Inhibitory Factor (MIF),a proinflammatory cytokine, has been shown to play an important role in the pathogenesis of sepsis, inflammation, and autoimmune disease. Recent studies indicated that MIF was markedly up-regulated in gastric ulcer. However,administration of a neutralizing antibody to MIF significantly attenuates the ulceration.These research support MIF is a key factor in pathogenesis of gastritis. Severe sepsis is commonly associated with multiple organ failure ,moreover , previous study demonstrated that lipopolysaccharide (LPS) caused gastric dysfunction. Protective effect of estrogen on gastritis have been demonstrated in some experimental models of gastritis.Likewise,many studies also suggest that estrogen exerts an anti- inflammatory activity. These previous observations led us to examine the effects of estrogen on MIF and the pathogenesis of gastritis in sepsis-induced rats. We were also interested in whether glabridin has estrogen-like effect.
Our results show that when LPS was given for 10 hours, the expressions of MIF in the OVX(ovariectomy) rats were higher than in the sham rats. On the other hand, treatment with estradiol was able to reverse OVX-induced increase in MIF levels. As expected, we find that induction of other proinflammatory mediators(TNF-α,IL-1β,iNOS) is positive related to MIF production. Data also show that levels of the antioxidant glutathione (GSH) were higher in rats treated with estradiol.Moreover, the estrogen-like effects of glabridin were tested in our experiments.Glabridin has greater anti-inflammatory propertie,and its antioxidant effect was significantly higher than estradiol.If we combine glabridin with tamoxifen we can see that tamoxifen partial reverse estradiol’s ability to inhibit inflammatory response. This suggests that the effect of glabridin is probably mediated by estrogen receptor.
In summary, it appears that estrogen and glabridin play a protective role in sepsis-induced gastritis.This study not only emphasizes the effect of estrogen,but also provides new insight into the drug development for sepsis.
論文目次 考試合格證明書
致謝 ...................................................I
目錄 ...................................................II
圖目錄 .................................................III
中文摘要 ...............................................1
英文摘要 ...............................................3
縮寫表 .................................................5
壹、研究背景 ...........................................6
貳、實驗材料與方法 .....................................19
參、實驗結果 ...........................................31
肆、討論 ...............................................38
伍、結論 ...............................................47
參考文獻 ...............................................49
附圖 ...................................................59
作者簡歷 ...............................................84
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