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目的探讨槲皮素对大鼠肝细胞胆固醇代谢的影响及相关机制。方法灌胃给予大鼠高脂乳剂1w,建立大鼠高脂血症模型,实验结束后,无菌条件下眼眶取血,离心取血清。采用含0、10μmol/L槲皮素的10%胎牛血清培养液干预培养BRL肝细胞24h,换液,用含0、10μmol/L槲皮素的10%高脂血清培养液干预培养BRL肝细胞48h,测定培养液中总胆固醇(total cholesterol,TC)、游离胆固醇(free cholesterol,FCH)、胆固醇酯(cholesterol ester,CE)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C),细胞内TC、FCH、CE的含量和调节胆固醇代谢的蛋白质,以及关键酶的表达与活性变化。结果与对照组相比较,10μmol/L槲皮素组培养液中TC、FCH和CE的浓度较低,且差异有统计学意义(P<0.05),槲皮素降低了LDL-C浓度,降低细胞内TC和FCH的浓度,升高细胞内CE含量,同时调节胆固醇代谢相应的酶和蛋白质,如羟甲基戊二酸单酰辅酶A还原酶(HMG-Co A Reductase,HMGCR)活性及其m RNA和蛋白质的表达水平较低,低密度脂蛋白受体(low-density lipoprotein receptor,LDLR)、胆固醇调节结合蛋白2(Sterol regulatory element-binding protein-2,SREBP-2)、三磷酸腺苷结合盒转运蛋白A1(ATP-binding cassette transporter A1,ABCA1)、肝X受体α(liver X receptorα,LXRα)m RNA和蛋白质的表达水平较高,且差异都具有统计学意义(P<0.05)。结论在高脂环境下,槲皮素可通过调节HMGCR、LDLR SREBP-2、ABCA1和LXRα的表达来调节胆固醇的代谢。
Objective To investigate the effect of quercetin on cholesterol metabolism in rat hepatocytes and its related mechanisms. Methods The rat model of hyperlipidemia was established by intragastric administration of high-fat emulsion for one week. After the experiment, blood was collected from orbital orbital in aseptic conditions and serum was taken by centrifugation. BRL hepatocytes were cultured with 10% fetal bovine serum containing 0 and 10 μmol / L quercetin for 24 h, and the liquid was changed. The BRL liver was intervened by 10% high fat serum containing 0 and 10 μmol / L quercetin The total cholesterol (TC), free cholesterol (FCH), cholesterol ester (CE), low-density lipoprotein cholesterol (LDL-C) , Intracellular TC, FCH, CE content and cholesterol metabolism regulating protein, as well as the key enzyme expression and activity changes. Results Compared with the control group, the concentration of TC, FCH and CE in the 10μmol / L Quercetin group was lower than that in the control group (P <0.05), and the concentration of quercetin reduced the LDL-C concentration and decreased Concentration of intracellular TC and FCH, increase intracellular CE content, and simultaneously regulate cholesterol-metabolizing enzymes and proteins such as HMG-CoA reductase (HMGCR) activity and their The mRNA and protein expression of m RNA and protein were low, and the expression of low-density lipoprotein receptor (LDLR), Sterol regulatory element-binding protein-2 (SREBP-2) The mRNA and protein expressions of ABCA1 and LXRα in liver were higher than those in control group (P <0.05). Conclusions Quercetin regulates cholesterol metabolism by regulating the expression of HMGCR, LDLR SREBP-2, ABCA1 and LXRα in hyperlipidemic environment.