食品科学 ›› 2018, Vol. 39 ›› Issue (19): 134-140.doi: 10.7506/spkx1002-6630-201819021

• 营养卫生 • 上一篇    下一篇

表没食子儿茶素没食子酸酯体内外调节大鼠胆固醇代谢的机制

葛 建,林 芳,张永勇,邓同乐,胡华军,刘 军   

  1. 中国计量大学生命科学学院,浙江 杭州 310018
  • 出版日期:2018-10-15 发布日期:2018-10-24
  • 基金资助:
    国家自然科学基金青年科学基金项目(31100499);中国博士后科学基金项目(2014M561766)

In Vivo and in Vitro Investigation of the Mechanism by Which Epigallocatechin Gallate Regulates Cholesterol Metabolism in Rats

GE Jian, LIN Fang, ZHANG Yongyong, DENG Tongle, HU Huajun, LIU Jun   

  1. College of Life Sciences, China Jiliang University, Hangzhou 310018, China
  • Online:2018-10-15 Published:2018-10-24

摘要: 目的:探讨表没食子儿茶素没食子酸酯(epigallocatechin gallate,EGCG)对大鼠胆固醇代谢的影响及相 关机制。方法:在建立Caco-2细胞和大鼠肝细胞培养以及Wistar大鼠高脂模型基础上,研究胆汁酸跨膜转运抑制、 胆固醇摄取和外排、血清胆固醇水平变化以及胆固醇代谢相关基因表达水平,探讨EGCG对大鼠胆固醇代谢可能 的调节机制。结果:EGCG显著抑制甘氨胆酸钠和牛磺胆酸钠在Caco-2细胞内的跨膜转运(P<0.05);显著干预 Caco-2细胞对胆固醇的摄取(P<0.05),同时增强胆固醇在大鼠肝细胞中的外排。动物实验结果表明:EGCG组大 鼠血清中总胆固醇、甘油三酯及低密度脂蛋白胆固醇浓度与模型组相比显著下降(P<0.05),高密度脂蛋白胆 固醇浓度明显升高(P<0.05);肝脏苏木精-伊红染色显示EGCG组大鼠肝细胞脂肪变性程度降低;与模型组相 比,EGCG组大鼠肝脏中羟甲基戊二酸单酰辅酶A还原酶表达水平较低;胆固醇调节结合蛋白2、肝脏X受体α和 胆固醇7α羟化酶基因表达水平显著升高(P<0.05)。结论:EGCG对体内胆固醇代谢的调节机制与其抑制肠道 胆汁酸重吸收、干扰胆固醇摄取、增强肝脏胆固醇外排以及调控相关基因表达有关,EGCG对胆固醇代谢具有综 合调节功能。

关键词: 表没食子儿茶素没食子酸酯, 胆汁酸重吸收, 胆固醇摄取, 胆固醇外排, 调节机制

Abstract: Objective: This study aimed to clarify the regulatory effect and the mechanism of action of epigallocatechin gallate (EGCG) on cholesterol metabolism in rats. Methods: In vitro cell culture models (Caco-2 cells and BRL hepatocytes) and hyperglycemic rat model were established. In order to determine the possible mechanism for the regulation of cholesterol metabolism in rats by EGCG, the inhibition of bile acids across Caco-2 cell monolayers, the influx and efflux of cholesterol, serum cholesterol level and the expression of lipid metabolism-related genes were evaluated. Results: The transport of sodium glycocholate and sodium taurocholate across Caco-2 cell monolayers was significantly inhibited by EGCG (P < 0.05). EGCG also inhibited the influx of cholesterol in Caco-2 and increased the efflux of cholesterol from rat hepatocytes. The results of animal tests revealed that serum total cholesterol, triglyceride and low-density lipoprotein cholesterol levels were significantly lower in the EGCG-treated group than in the high-fat diet model group (P < 0.05), while high-density lipoprotein cholesterol levels were significantly higher (P < 0.05). Hematoxylin and eosin staining of the rat liver showed that liver steatosis was significantly attenuated by EGCG (P < 0.05). At the molecular level, the mRNA and protein expression of hydroxy methylglutaryl-CoA reductase were significantly decreased in the EGCG-treated group when compared with the model group, while the mRNA and protein expression levels of sterol regulatory element-binding protein-2, liver X receptor α and cholesterol 7α hydroxylase were significantly increased (P < 0.05). Conclusion: EGCG had multiple regulatory effects on cholesterol metabolism, and the underlying mechanism was attributed to the inhibition of bile acid re-absorption, the blocking of cholesterol influx, and the enhancement of cholesterol efflux as well as the regulation of the expression of cholesterol metabolism-related genes.

Key words: epigallocatechin gallate, reabsorption of bile acid, cholesterol uptake, cholesterol efflux, regulation mechanism

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