發(fā)布時(shí)間：2018-04-18 16:41

  本文選題：表沒(méi)食子兒茶素沒(méi)食子酸酯(EGCG) + p38絲裂原活化蛋白激酶　； 參考：《南京師范大學(xué)》2005年碩士論文

【摘要】：表沒(méi)食子兒茶素沒(méi)食子酸酯(EGCG)是綠茶多酚的主要活性成分,近年研究表明EGCG除具抗癌、抗氧化等活性外,尚具顯著抗炎活性,但其作用機(jī)理研究尚少。本文從p38 MAPK信號(hào)通路及炎癥因子表達(dá)方面研究了EGCG對(duì)脂多糖(LPS)介導(dǎo)炎癥過(guò)程的作用,在動(dòng)物急性肺損傷(ALI)模型的干預(yù)作用方面也探討了EGCG抗炎作用的可能機(jī)理。 1.體外EGCG對(duì)LPS的直接作用: 本研究首次應(yīng)用透射電鏡觀察及內(nèi)毒素鱟實(shí)驗(yàn)檢測(cè)法研究EGCG對(duì)LPS的直接作用,結(jié)果表明EGCG對(duì)INS的結(jié)構(gòu)和量無(wú)顯著影響,提示EGCG對(duì)LPS無(wú)直接作用。 2.EGCG對(duì)LPS激活的小鼠巨噬細(xì)胞的作用: 以LPS刺激小鼠巨噬細(xì)胞株RAW264.7,應(yīng)用Western blotting法檢測(cè)磷酸化p38 MAPK的表達(dá),EMSA法檢測(cè)細(xì)胞TNF-a和PGE_2的表達(dá)。結(jié)果表明EGCG對(duì)LPS激活的p38 MAPK磷酸化,TNF-a和PGE_2的表達(dá)均具明顯抑制作用。對(duì)小鼠腹腔巨噬細(xì)胞的免疫細(xì)胞化學(xué)實(shí)驗(yàn)同樣表明了EGCG對(duì)INS激活的p38MAPK通路的干預(yù)作用。 3.EGCG對(duì)小鼠油酸型ALI模型的干預(yù)作用: 本研究首次應(yīng)用小鼠油酸型ALI動(dòng)物模型研究EGCG的體內(nèi)效應(yīng)。EGCG于造模前給藥,劑量為6、12和25mg/kg,造模后檢測(cè)小鼠肺組織p38 MAPK磷酸化和血清TNF-a的表達(dá),結(jié)果表明EGCG對(duì)肺組織p38 MAPK磷酸化和血清TNF-a表達(dá)具有抑制作用。提示EGCG對(duì)油酸型ALI具有干預(yù)作用。 本研究結(jié)果表明EGCG對(duì)LPS無(wú)直接影響,可通過(guò)干預(yù)體內(nèi)信號(hào)通路發(fā)揮其抑制作用,p38 MAPK可能是EGCG抑制LPS誘導(dǎo)巨噬細(xì)胞表達(dá)TNF-a的重要通路之一。另外,EGCG對(duì)油酸型小鼠急性肺損傷有一定保護(hù)作用,其作用機(jī)制可能與其能抑制p38 MAPK的磷酸化,并減少TNF-a的合成與釋放有關(guān)。
[Abstract]:Epigallocatechin gallate (EGCG) is the main active component of green tea polyphenols. Recent studies have shown that EGCG not only has anti-cancer and anti-oxidation activities, but also has significant anti-inflammatory activity.In this paper, the effects of EGCG on lipopolysaccharide (LPS) -mediated inflammation were studied from the aspects of p38 MAPK signaling pathway and inflammatory factor expression. The possible mechanism of EGCG anti-inflammatory action was also discussed in the animal model of acute lung injury.1.Direct effect of EGCG on LPS in vitro:In this study, the direct effect of EGCG on LPS was studied by transmission electron microscopy and endotoxin Limulus test for the first time. The results showed that EGCG had no significant effect on the structure and quantity of INS, suggesting that EGCG had no direct effect on LPS.Effects of 2.EGCG on LPS activated mouse macrophages:Mouse macrophage cell line RAW264.7 was stimulated by LPS. The expression of phosphorylated p38 MAPK was detected by Western blotting method and the expression of TNF-a and PGE_2 was detected by EMSA method.The results showed that EGCG significantly inhibited the expression of LPS activated p38 MAPK phosphorylated TNF-a and PGE_2.The immunocytochemistry of murine peritoneal macrophages also demonstrated the effect of EGCG on the p38MAPK pathway activated by INS.The intervention effect of 3.EGCG on oleic acid type ALI model in mice:In this study, we used oleic acid ALI animal model to study the in vivo effect of EGCG. EGCG was administered at doses of 6 mg / kg and 25 mg / kg. The phosphorylation of p38 MAPK and the expression of TNF-a in serum were detected after the establishment of the model.The results showed that EGCG could inhibit the phosphorylation of p38 MAPK and the expression of serum TNF-a in lung tissues.The results suggest that EGCG can interfere with oleic acid type ALI.The results suggest that EGCG has no direct effect on LPS, and p38 MAPK may be one of the important pathways by which EGCG inhibits the expression of TNF-a in macrophages induced by LPS.In addition, EGCG has a protective effect on acute lung injury in oleic acid mice, and its mechanism may be related to the inhibition of phosphorylation of p38 MAPK and the reduction of synthesis and release of TNF-a.
【學(xué)位授予單位】：南京師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2005
【分類(lèi)號(hào)】：R363

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