利拉鲁肽对人HepG2肝细胞脂代谢的影响及作用机制
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新疆维吾尔自治区自然科学基金(2015211C182)


Effects of liraglutide on lipid metabolism in human HepG2 liver cells and its related mechanism
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    摘要:

    目的:建立HepG2肝细胞脂肪变性模型,了解利拉鲁肽是否可改善HepG2细胞内脂代谢状态,并对相关机制进行初步探讨。方法:软脂酸钠诱导建立HepG2肝细胞脂肪变性模型,并给予利拉鲁肽干预。油红O染色确定HepG2肝细胞脂肪变性模型的建立。Western blot检测HepG2 中脂质合成和分解关键酶蛋白水平的变化情况及HepG2 中PI3K信号通路活化情况。采用PI3K信号通路抑制剂预处理HepG2 细胞,观察PI3K信号通路在软脂酸钠诱导建立HepG2肝细胞脂肪变性中的作用。结果:油红O染色结果显示模型建立成功。Western blot结果显示,软脂酸钠诱导可显著升高HepG2中固醇调节元件结合蛋白1c(sterol regulatory element-binding protein1c,SREBP1c)-脂肪酸合成酶(fatty acid synthase,FAS)的蛋白水平,降低脂肪甘油三酯脂酶(adipose triglyceride lipase,ATGL)的蛋白水平(P < 0.01),并上调HepG2中PI3K信号通路活化水平;与软脂酸钠组相比,利拉鲁肽干预可显著降低HepG2中SREBP1c-FAS 的蛋白水平,升高ATGL的蛋白水平,并抑制HepG2中PI3K信号通路活化水平;阻断HepG2中的PI3K信号通路后,软脂酸钠诱导HepG2脂肪变性的能力显著降低(P < 0.01)。结论:利拉鲁肽可通过调节HepG2中的PI3K信号通路,进而改善HepG2细胞的脂代谢情况。

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    Objective:We established a HepG2 hepatic steatosis model to observe whether liraglutide improves lipid metabolism in HepG2 liver cells,and discuss the related mechanisms. Methods:Sodium palmitate was performed to induce HepG2 steatosis model,and liraglutide intervention was given. Oil Red O staining was performed to determine the establishment of HepG2 hepatic steatosis model. Key enzyme of lipid synthesis and degradation as well as the activation of PI3K signaling pathway in HepG2 liver cells were detected by Western blotting assay. To observe the effect of PI3K signaling pathway in sodium palmitate induced HepG2 hepatic steatosis,HepG2 liver cells was pretreated with PI3K signaling pathway inhibitor. Results:Oil Red O staining showed that the model was successfully established. Western blotting assay showed that sodium palmitate significantly increased the expression of sterol regulatory element-binding protein1c(SREBP1c)and fatty acid synthase(FAS)protein levels in HepG2 liver cells,and decreased adipose triglyceride lipase (ATGL)protein levels(P < 0.01); sodium palmitate activated PI3K signaling pathway in HepG2 liver cells. Compared with sodium palmitate,liraglutide significantly decreased the expression of SREBP1c and FAS protein levels in HepG2 liver cells,and increased ATGL protein levels; liraglutide inhibited PI3K signaling pathway in HepG2 liver cells. After blocking PI3K signaling pathway,sodium palmitate-induced steatosis of HepG2 liver cells was significantly reduced (P < 0.01). Conclusion:By regulating PI3K signaling pathway in HepG2 liver cells,liraglutide improves lipid metabolism in HepG2 liver cells.

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朱红霞,高 静,邓晓龙,朱 筠.利拉鲁肽对人HepG2肝细胞脂代谢的影响及作用机制[J].南京医科大学学报(自然科学版),2015,(9):1211-1215

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  • 收稿日期:2015-03-25
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  • 在线发布日期: 2015-09-10
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