本文選題：S-腺苷蛋氨酸　切入點(diǎn)：內(nèi)毒素　出處：《重慶醫(yī)科大學(xué)》2010年碩士論文　論文類型：學(xué)位論文

【摘要】： 目的通過建立內(nèi)毒素性肝損害的動物模型,觀察S-腺苷蛋氨酸(S-adenosylmethionine, SAM)預(yù)處理對脂多糖(Lipopolysaccharide, LPS)作用下小鼠肝臟的肝X受體(Liver X receptors, LXR)α和Toll樣受體4(Toll like receptor 4, TLR4)以及炎癥通路中重要的下游促炎細(xì)胞因子腫瘤壞死因子α(TNF-α)和抑炎細(xì)胞因子白細(xì)胞介素10(IL-10)表達(dá)的影響,探討SAM減輕LPS作用下肝臟的損傷和其作用相關(guān)的可能機(jī)制。 方法實(shí)驗(yàn)小鼠隨機(jī)均分為三組,NS組:腹腔注射等體積生理鹽水,LPS組:腹腔注射劑量為10mg/kg的LPS,SAM組:腹腔注入10mg/kg的LPS前2h于小鼠腹腔內(nèi)注射100mg/kg的SAM。記錄三組小鼠120h存活率;光鏡和電鏡觀察組織病理學(xué)改變;酶聯(lián)免疫吸附法(ELISA)檢測血清中TNF-α和IL-10的濃度;免疫組織化學(xué)法(SABC)和蛋白免疫印跡法(Western blot)檢測肝組織中TLR4和LXRα的蛋白表達(dá)水平;按數(shù)據(jù)類型進(jìn)行統(tǒng)計(jì)學(xué)分析。 結(jié)果S-腺苷蛋氨酸能明顯提高小鼠存活率,SAM組為50.0%,LPS組為30.0%,差異有統(tǒng)計(jì)學(xué)意義(P0.05);光鏡和電鏡觀察比較小鼠肝臟組織病理損害程度,SAM有效的減輕了內(nèi)毒素性肝損害;SAM組血清中TNF-α水平( 718.83±53.27 ) pg/ml顯著低于LPS組(1791.79±122.19)pg/ml,差異有統(tǒng)計(jì)學(xué)意義(P0.05);SAM組血清中IL-10(418.69±38.77)pg/ml增加且高峰前移,與LPS組(347.09±31.37)pg/ml比較差異有統(tǒng)計(jì)學(xué)意義(P0.05);免疫組織化學(xué)法(SABC)觀察和蛋白免疫印跡法(Western blot)檢測,SAM組肝組織中LXRα(1.605±0.027)表達(dá)明顯增加,而TLR4(1.365±0.017)表達(dá)則明顯減少,兩者與LPS組LXRα(1.375±0.014)和TLR4(1.550±0.034)比較差異均有統(tǒng)計(jì)學(xué)意(P0.05)。 結(jié)論SAM能明顯減輕LPS所致的肝損害,其機(jī)制可能與其降低肝臟各種細(xì)胞TLR4的表達(dá),增強(qiáng)LXRα的表達(dá),最終導(dǎo)致TNF-α水平降低和IL-10水平增高有關(guān)。
[Abstract]:Objective to establish an animal model of liver injury induced by endotoxin. The effects of S-adenosylmethionine (SAM) preconditioning on lipopolysaccharide (LPSs) induced by lipopolysaccharide in lipopolysaccharide (LPSs) induced by lipopolysaccharide in lipopolysaccharide (lipopolysaccharide) in lipopolysaccharide (lipopolysaccharide) in lipopolysaccharide (LPSs) in lipopolysaccharide (lipopolysaccharide) were observed in mice liver X receptor (LXR) 偽 and Toll like receptor 4 Toll like receptor 4 (TLR4), as well as the important downstream inflammatory cytokine TNF- 偽 in inflammatory pathway. And the expression of interleukin-10 (IL-10), an anti-inflammatory cytokine, To investigate the possible mechanism of SAM in alleviating liver injury induced by LPS. Methods the experimental mice were randomly divided into three groups: intraperitoneal injection of normal saline LPS group: 10 mg / kg LPS-1 SAM group: 10 mg / kg LPS 2 hours before intraperitoneal injection of 100 mg / kg SAM. The 120h survival rate of the three groups was recorded. The histopathological changes were observed by light and electron microscopy, the concentrations of TNF- 偽 and IL-10 in serum were detected by Elisa, the protein expression of TLR4 and LXR 偽 in liver tissue was detected by immunohistochemistry and Western blot. Statistical analysis was carried out according to data type. Results S- adenosine methionine could significantly improve the survival rate of mice. The survival rate of SAM group was 50. 0 and that of LPS group was 30. 0, the difference was statistically significant (P 0. 05). The pathological damage degree of liver tissue in mice was observed by light microscope and electron microscope. The level of TNF- 偽 in serum of SAM group (718.83 鹵53.27 ng / ml) was significantly lower than that of LPS group (1791.79 鹵122.19 ng / ml). The difference was statistically significant. The serum TNF- 偽 level of SAM group increased and the peak peak moved forward. Compared with LPS group (347.09 鹵31.37 g / ml), the expression of LXR 偽 _ (1.605 鹵0.027) in liver tissue was significantly increased by immunohistochemistry and the expression of LXR _ 偽 _ (1.605 鹵0.027) was decreased by Western blotanalysis, while the expression of LXR 偽 _ (1.605 鹵0.027) was significantly decreased in LPS group, while the expression of LXR _ 偽 _ (1.605 鹵0.027) was significantly decreased by immunohistochemistry and Western blotting. There were significant differences between the two groups in terms of LXR 偽 (1.375 鹵0.014) and TLR4(1.550 鹵0.034 (P 0.05). Conclusion SAM can attenuate the liver damage induced by LPS, and its mechanism may be related to the decrease of TLR4 expression and the enhancement of LXR 偽 expression in various liver cells, which leads to the decrease of TNF- 偽 level and the increase of IL-10 level.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2010
【分類號】：R363

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