AcSDKP对非酒精性脂肪性肝炎体外模型脂质代谢功能的影响及分子机制研究
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新疆维吾尔自治区自然科学基金项目(2021D01C355)


Effect of AcSDKP on lipid metabolism in NASH model and its molecular mechanism
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    摘要:

    目的 探究N-乙酰-丝-天冬-赖-脯氨酸(AcSDKP)对游离脂肪酸(FFA)诱导人肝细胞L02的非酒精性脂肪性肝炎(NASH)体外模型脂质代谢功能的影响及机制。方法 将L02细胞分为对照(NC)组、FFA组和不同浓度AcSDKP处理组(FFA+1 nM AcSDKP组、FFA+10 nM AcSDKP组、FFA+100 nM AcSDKP组),油红O染色检测各组L02细胞脂质沉积,试剂盒检测各组L02细胞中甘油三酯(TG)含量,ELISA实验检测各组L02细胞上清液中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平及丙二醛(MDA)含量,Annexin V-FITC/PI 双染法检测各组L02细胞凋亡率,实时荧光定量PCR和Western blot分析各组L02细胞中腺苷酸活化蛋白激酶(AMPK)、脂肪酸合成酶(FASN)、甾醇调节元件结合蛋白-1c(SREBP-1c)mRNA与蛋白的水平。结果 与FFA组比较,FFA+1 nM AcSDKP组、FFA+10 nM AcSDKP组、FFA+100 nM AcSDKP组L02细胞中脂滴沉积明显减少,ALT、AST水平显著降低(P<0.05),MDA含量显著减少(P<0.05),细胞凋亡率显著降低(P<0.05),AMPK mRNA相对表达量和蛋白相对表达量显著上调(P<0.05),FASN和SERSP-1c mRNA相对表达量和蛋白相对表达量显著下调(P<0.05)。且与FFA+1 nM AcSDKP组和FFA+10 nM AcSDKP组比较,FFA+100 nM AcSDKP组L02细胞中脂质沉积更少,ALT、AST水平也显著降低(P<0.05),MDA含量显著减少(P<0.05),细胞凋亡率进一步降低(P<0.05),同时,AMPK蛋白相对表达量显著上调(P<0.05),FASN和SERSP-1c mRNA相对表达量和蛋白相对表达量显著下调(P<0.05)。结论 AcSDKP能够减少FFA诱导人肝细胞L02内脂质沉积,促进细胞脂质代谢并抑制细胞凋亡,该作用可能与其调节AMPK/FASN/SERSP-1c表达有关

    Abstract:

    Objective To investigate the effects of N-acetyl-filament-aspartate-Lyophil-proline (AcSDKP) on lipid metabolism in vitro model of nonalcoholic steatohepatitis (NASH) induced by free fatty acid (FFA) in human hepatocyte L02 and its mechanism. Methods L02 cells were divided into control (NC) group, FFA group and AcSDKP treatment groups with different concentrations (FFA+1nM AcSDKP group, FFA+10nM AcSDKP group, FFA+100nM AcSDKP group), lipid deposition of L02 cells in each group was detected by oil red O staining, the content of triglyceride (TG) in L02 cells of each group was detected by the kit, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and malondialdehyde (MDA) in the supernatant of L02 cells of each group were detected by ELISA, the apoptosis rate of L02 cells of each group was detected by Annexin V-FITC/PI double staining method, the mRNA and protein levels of adenylate activated protein kinase (AMPK), fatty acid synthetase (FASN) and sterol regulatory element binding protein-1c (SREBP-1c) in L02 cells of each group were analyzed by real-time fluorescence quantitative PCR and Western blot analysis. Results Compared with FFA group, lipid droplets deposition in L02 cells in FFA+1nM AcSDKP group, FFA+10nM AcSDKP group and FFA+100nM AcSDKP group were significantly decreased, the level of ALT and AST were significantly decreased (P<0.05). MDA content was significantly decreased (P<0.05), apoptosis rate was significantly decreased (P<0.05), AMPK mRNA relative expression level and protein relative expression level were significantly up-regulated (P<0.05), FASN and SERSP-1c mRNA relative expression level and protein relative expression level were significantly down-regulated (P<0.05). Moreover, compared with FFA+1nM AcSDKP group and FFA+10nM AcSDKP group, the lipid deposition in L02 cells in FFA+100nM AcSDKP group was less, and the levels of ALT and AST were also significantly decreased (P<0.05), MDA content was significantly decreased (P<0.05), the apoptosis rate was further decreased (P<0.05), while AMPK protein relative expression was significantly up-regulated (P<0.05), FASN and SERSP-1c mRNA relative expression and protein relative expression were significantly down-regulated (P<0.05). Conclusion AcSDKP can reduce lipid deposition in L02 induced by FFA, promote lipid metabolism and inhibit cell apoptosis, which may be related to the regulation of AMPK/FASN/SERSP-1c expression

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  • 在线发布日期: 2024-12-20
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