本文選題：血管生成素相關(guān)蛋白3 + 肝X受體　； 參考：《重慶醫(yī)科大學》2008年碩士論文

【摘要】： 目的:觀察不同葡萄糖濃度對人肝細胞(L02)內(nèi)膽固醇合成及HMGCR、LXRα和ANGPTL3基因表達的影響;并在各組加入辛伐他汀干預,進一步說明上述影響作用,研究它們對ANGPTL3基因表達影響的機制,及ANGPTL3在代謝綜合征發(fā)生中的作用。 方法:以L02為研究對象,一組在含不同濃度葡萄糖的培養(yǎng)液中培養(yǎng)24小時;另外一組在含10μmol/L辛伐他汀的不同濃度葡萄糖培養(yǎng)液中培養(yǎng)24小時。采用膽固醇酶聯(lián)試劑盒檢測細胞內(nèi)膽固醇含量,逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)(RT-PCR)技術(shù)檢測L02細胞HMGCR、LXRα和ANGPTL3的mRNA水平,用免疫印跡技術(shù)檢測L02細胞ANGPTL3蛋白質(zhì)的表達水平。 結(jié)果:高濃度葡萄糖培養(yǎng)的L02細胞內(nèi)膽固醇含量明顯高于正常葡萄糖濃度培養(yǎng)組(P0.05),且細胞內(nèi)LXRα、ANGPTL3 mRNA和ANGPTL3蛋白質(zhì)表達量也明顯高于正常組(P0.05),HMGCR在各組的表達差異無統(tǒng)計學意義(P0.05)。在辛伐他汀干預下,LXRα、ANGPTL3 mRNA和ANGPTL3蛋白質(zhì)表達量均較未加辛伐他汀組下降(P0.05);膽固醇含量也明顯低于未加辛伐他汀組(P0.05);HMGCR表達量也明顯低于未加辛伐他汀組(P0.05)。在辛伐他汀干預下,不同葡萄糖濃度組的L02細胞內(nèi)LXRα、ANGPTL3 mRNA和ANGPTL3蛋白表達量及膽固醇含量依然與葡萄糖濃度正相關(guān)。 結(jié)論:葡萄糖能增加L02細胞內(nèi)膽固醇含量,上調(diào)LXRα和ANGPTL3的表達。辛伐他汀能通過減少細胞內(nèi)膽固醇的合成抑制葡萄糖對LXRα和ANGPTL3的上調(diào)作用。高濃度葡萄糖增加ANGPTL3表達的途徑可能是通過增加細胞內(nèi)總膽固醇含量激活LXRα,而LXRα則引起ANGPTL3 mRNA和蛋白質(zhì)高表達。糖尿病和脂代謝紊亂可能通過LXRα和ANGPTL3聯(lián)系起來,ANGPTL3表達量與代謝綜合征有關(guān)。
[Abstract]:Aim: to observe the effects of different glucose concentrations on cholesterol synthesis and the expression of LXR 偽 and ANGPTL3 genes in human hepatocytes, and to investigate the effects of simvastatin on the expression of ANGPTL3 gene. And the role of ANGPTL3 in metabolic syndrome. Methods: L02 was cultured in different concentrations of glucose for 24 hours in one group and in different concentrations of simvastatin in 10 渭 mol/L for 24 hours in the other group. The cholesterol content in L02 cells was detected by enzyme linked assay kit, the mRNA levels of LMGCR-LXR 偽 and ANGPTL3 in L02 cells were detected by reverse transcription-polymerase chain reaction (RT-PCR), and the expression of ANGPTL3 protein in L02 cells was detected by Western blotting. Results: the cholesterol content in L02 cells cultured with high glucose concentration was significantly higher than that in normal glucose culture group (P 0.05), and the expression of LXR 偽 -ANGPTL3 mRNA and ANGPTL3 protein in L02 cells was significantly higher than that in normal group (P 0.05). Under the intervention of simvastatin, the protein expression of LXR 偽 -ANGPTL3 mRNA and ANGPTL3 were significantly lower than that of untreated simvastatin group (P 0.05), and the cholesterol content was significantly lower than that of untreated simvastatin group (P 0.05) and HMGCR expression was also significantly lower than that of untreated simvastatin group (P 0.05). Under the intervention of simvastatin, the expression of LXR 偽 -ANGPTL3 mRNA and ANGPTL3 protein and cholesterol in L02 cells with different glucose concentrations were still positively correlated with glucose concentration. Conclusion: glucose can increase cholesterol content and up-regulate the expression of LXR 偽 and ANGPTL3 in L02 cells. Simvastatin inhibited the up-regulation of LXR 偽 and ANGPTL3 by reducing the synthesis of intracellular cholesterol. High concentration of glucose may increase the expression of ANGPTL3 through the activation of LXR 偽 by increasing the total cholesterol content in the cells, while LXR 偽 leads to the high expression of ANGPTL3 mRNA and protein. Diabetes mellitus and lipid metabolism disorder may be associated with the expression of ANGPTL3 by LXR 偽 and ANGPTL3.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2008
【分類號】：R341

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