苜蓿皂苷对大鼠肝脏及肝脏细胞低密度脂蛋白受体、三磷酸腺苷结合盒转运体mRNA表达的影响

本试验旨在研究苜蓿皂苷对大鼠肝脏及大鼠肝脏细胞(BRL细胞)胆固醇清除和转运途径中关键基因低密度脂蛋白受体(LDLR)、三磷酸腺苷结合盒转运体G5(ABCG5)、三磷酸腺苷结合盒转运体G8(ABCG8)mRNA表达量的影响,从个体和细胞水平初步探讨苜蓿皂苷调控胆固醇清除和转运的分子机制。采用高脂饲粮建立大鼠高脂模型,测定苜蓿皂苷对正常、高脂大鼠血清指标[总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)含量]和肝脏LDLR、ABCG5、ABCG8 mRNA表达量的影响;采用高糖DMEM培养液建立BRL细胞脂变模型,测定苜蓿皂苷浓度对BRL细胞活性的影响,测定苜蓿皂苷对正常、脂变细胞LDLR、ABCG5、ABCG8 mRNA表达量的影响。结果表明:1)苜蓿皂苷显著降低高脂大鼠血清中TG、TC和LDL-C的含量(P0.05);2)苜蓿皂苷显著上调正常大鼠肝脏LDLR、ABCG5、ABCG8及高脂大鼠ABCG5、ABCG8 mRNA表达量(P0.05);3)添加200、250μg/m L苜蓿皂苷显著提高了BRL细胞的活性(P0.05);4)苜蓿皂苷显著上调正常BRL细胞LDLR、ABCG5、ABCG8 mRNA表达量(P0.05),而对脂变BRL细胞各基因mRNA表达量无显著影响(P0.05)。结果提示,苜蓿皂苷可通过调控LDLR、ABCG5、ABCG8 mRNA的表达来增加肝细胞内胆固醇的清除和转运,从而降低机体胆固醇的含量。

Effects of Alfalfa Saponins on mRNA Expressions of Low-Density Lipoprotein Receptor and Adenosine Triphosphate Binding Cassette Transporters in Liver and Liver Cells of Rats

This experiment was conducted to investigate the effects of alfalfa saponins ( AS) on mRNA expres-sions of low-density lipoprotein receptor ( LDLR) , adenosine triphosphate binding cassette transporter G5 ( AB-CG5) and adenosine triphosphate binding cassette transporter G8 ( ABCG8) in liver and liver cells of rats, and discuss the mechanism of AS regulating cholesterol elimination and transportation at both individual and cellular levels. Hyperlipidemic rat model was set up using high fat diet, and the effects of AS on serum indexes [ total cholesterol ( TC) , triglyceride ( TG) , low-density lipoprotein cholesterol ( LDL-C) and high-density lipopro-tein cholesterol ( HDL-C) contents] and liver LDLR, ABCG5 and ABCG8 mRNA expressions of normal and hyperlipidemic rats were determined;hyperlipidemic cell model was set up using high DMEM culture medium, the effects of AS concentration on BRL cell activity, and AS on LDLR, ABCG5 and ABCG8 mRNA expres-sions of normal and hyperlipidemic cells were determined. The results showed as follows:1) AS significantly decreased the contents of triglyceride, total chelesterol and low-density lipoprotein cholesterol in serum of hy-perlipidemic rats ( P<0.05);2) AS significantly up-regulated mRNA expressions of LDLR, ABCG5 and AB-CG8 in liver of normal rats and those of ABCG5 and ABCG8 in liver of hyperlipidemic rats ( P<0.05);3) the supplementation of 200 and 250 μg/mL AS increased BRL cell activity ( P<0.05); 4) AS significantly up-regulated mRNA expressions of LDLR, ABCG5 and ABCG8 of normal BRL cells (P<0.05), however, AS had no significant effects on those of hyperlipidemic BRL cells. The results indicate that AS may accelerate the elimination and transportation of cholesterol by up-regulating mRNA expressions of LDLR, ABCG5 and AB-CG8, and then reduce the content of cholesterol in body.