本文選題：脂氧素 + 肝纖維化��； 參考：《南昌大學(xué)》2014年碩士論文

【摘要】：目的：脂氧素（Lipoxins，LXs）是一類(lèi)新發(fā)現(xiàn)的花生四烯酸代謝產(chǎn)物，具有強(qiáng)大的抗炎與促炎癥消退雙重作用，是體內(nèi)重要的內(nèi)源性促炎癥消退介質(zhì)，而且我們的前期研究工作提示LXs具備護(hù)肝效應(yīng)。在本研究中我們利用CCl4建立實(shí)驗(yàn)性肝纖維化大鼠模型，觀察LXs受體激動(dòng)劑BML-111對(duì)肝纖維化的保護(hù)作用，，并探討其可能作用機(jī)制。 方法：Sprague-Dawley（SD）大鼠皮下注射CCl4建立大鼠實(shí)驗(yàn)性肝纖維化模型。大鼠肝組織切片HE染色觀察肝組織損傷和炎癥細(xì)胞浸潤(rùn)程度。血清AST（Aspartate transaminase）與ALT（Alanine transaminase）活性檢測(cè)反映肝功能水平。肝臟大體觀、肝組織切片VG染色和Masson染色、生化試劑盒檢測(cè)肝組織Hyp（Hydroxyproline）含量綜合評(píng)定肝纖維化程度。免疫組化和Western-blot法檢測(cè)肝臟組織α-SAM（α-sooth muscle actin）表達(dá)水平。TGF-β1（Transforminggrowth factor-β1）及PDGF（Platelet derived growth factor）的表達(dá)水平通過(guò)ELISA和Western-blot法測(cè)定。 Western-blot法檢測(cè)肝組織中MMP-2（Matrixmetalloproteinase-2）、MMP-3、MMP-7、MMP-9及TIMP-1（Tissueinhibitors ofmetalloproteinase-1）的表達(dá)水平。肝組織MDA（Malondialdehyde）含量，SOD（Superoxide dismutase）、GSH-Px（Glutathione peroxidase）、CAT（Catalase）活性和肝組織總抗氧化能力T-AOC（Total antioxidant capacity）分別利用生化試劑盒進(jìn)行檢測(cè)。免疫熒光法檢測(cè)NF-κB（Nuclear factor κB）P65的核轉(zhuǎn)位水平。 結(jié)果：BML-111能夠抑制大鼠肝臟損傷、炎癥細(xì)胞浸潤(rùn)和肝功能損害；減輕大鼠的肝纖維化程度；抑制大鼠HSC（Hepatic stellate cell）活化；抑制大鼠肝組織表達(dá)TGF-β1和PDGF；降低MMP-2、MMP-3、MMP-7、MMP-9和TIMP-1的表達(dá)水平；減少M(fèi)DA含量，但增加SOD、GSH-Px、CAT抗氧化酶的活性以及肝組織總抗氧化能力T-AOC；抑制大鼠NF-κB P65核轉(zhuǎn)位。 結(jié)論：BML-111具有保護(hù)CCl4誘導(dǎo)的大鼠實(shí)驗(yàn)性肝纖維化效應(yīng)。其作用機(jī)制可能包括減少促纖維化細(xì)胞因子TGF-β1和PDGF的表達(dá)、抑制HSC活化而減少ECM合成、增強(qiáng)大鼠肝組織抗氧化能力、恢復(fù)MMPs/TIMPs平衡而調(diào)節(jié)ECM的異常代謝、阻礙轉(zhuǎn)錄因子NF-κB P65核轉(zhuǎn)位。
[Abstract]:Objective: lipoxygenin (LXs) is a newly discovered metabolite of arachidonic acid, which has both anti-inflammatory and pro-inflammatory effects, and is an important endogenous mediator of inflammatory regression in vivo. Furthermore, our previous studies suggest that LXs has the effect of protecting liver. In this study, we used CCl4 to establish an experimental rat model of hepatic fibrosis, to observe the protective effect of LXs receptor agonist BML-111 on hepatic fibrosis and to explore its possible mechanism. Methods the experimental hepatic fibrosis model was established by subcutaneously injection of CCl4 into the SD rats of Sprague-Dawley (SD) rats. Liver tissue injury and inflammatory cell infiltration were observed by HE staining in rat liver tissue sections. The detection of serum AST(Aspartate transaminase and ALT(Alanine transaminase activity reflects the level of liver function. Liver gross, liver tissue sections VG staining and Masson staining, biochemical kit detection of liver tissue Hypo Hydroxyproline) comprehensive evaluation of the degree of liver fibrosis. The expression of 偽 -SAM (偽 -sooth muscle tin.TGF- 尾 1(Transforminggrowth factor- 尾 1) and the expression of PDGF(Platelet derived growth factor) were detected by ELISA and Western-blot methods. The expression of MMP-2, matrix metalloproteinase-2, MMP-3, MMP-7, MMP-9 and TIMP-1(Tissueinhibitors of metalloproteinase-1 in liver tissue were detected by Western-blot. The activity of GSH-PxGlutathione peroxidase and the total antioxidant capacity (T-AOC(Total antioxidant capacityof liver tissue) were determined by biochemical kit. The nuclear translocation of NF- 魏 B(Nuclear factor 魏 B)P65 was detected by immunofluorescence assay. Results: the expression of TGF- 尾 1 and PDGF- 尾 1, MMP-2 MMP-3, MMP-7, MMP-9 and TIMP-1 in rat liver were inhibited by WBML-111, the liver injury, inflammatory cell infiltration and liver function damage were inhibited, the degree of hepatic fibrosis was alleviated, the activation of rat HSC(Hepatic stellate cell was inhibited, and the expression of MMP-2-MMP-3, MMP-7, MMP-9 and TIMP-1 were decreased. The content of MDA was decreased, but the activity of SOD GSH-PxX cat and the total antioxidant capacity of liver tissue were increased, and the nuclear translocation of NF- 魏 B p65 was inhibited. Conclusion: BML-111 has protective effect on experimental hepatic fibrosis induced by CCl4 in rats. The mechanism may include reducing the expression of TGF- 尾 1 and PDGF, inhibiting the activation of HSC and decreasing the synthesis of ECM, enhancing the antioxidant ability of rat liver tissue, restoring the balance of MMPs/TIMPs and regulating the abnormal metabolism of ECM. Block the nuclear translocation of NF- 魏 B p65.
【學(xué)位授予單位】：南昌大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R575.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前6條

1 姜雪強(qiáng);鄒小靜;田德英;;脂氧素A_4對(duì)大鼠急性肝衰竭的保護(hù)作用[J];中國(guó)組織化學(xué)與細(xì)胞化學(xué)雜志;2010年06期

2 周曉燕;張力;吳萍;熊維;李詠生;葉篤筠;;脂氧素對(duì)巨噬細(xì)胞表面免疫抑制分子和共刺激分子表達(dá)的影響[J];華中科技大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2007年03期

3 周曉燕;徐方云;蔡震宇;王紅梅;祝子瑞;吳萍;葉篤筠;;脂氧素A_4對(duì)脂多糖誘導(dǎo)巨噬細(xì)胞氧化損傷的影響[J];細(xì)胞生物學(xué)雜志;2009年03期

4 張力;吳萍;萬(wàn)敬員;周曉燕;熊維;袁萍;李詠生;葉篤筠;;脂氧素對(duì)Jurkat T細(xì)胞增殖和白細(xì)胞介素-2/白細(xì)胞介素-2受體表達(dá)的影響[J];中國(guó)病理生理雜志;2008年01期

5 ;Lipoxin A_4 negatively regulates lipopolysaccharide-induced differentiation of RAW264.7 murine macrophages into dendritic-like cells[J];Chinese Medical Journal;2007年11期

6 ;Clinical observation of salvianolic acid B in treatment of liver fibrosis in chronic hepatitis B[J];World Journal of Gastroenterology;2002年04期

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