蓝靛果花色苷对高脂血症大鼠肝脏LDLR、ABCG1及ABCA1基因表达的影响

Effect of Lonicera caerulea Anthocyanins on the Expression of LDLR, ABCG1 and ABCA1 Genes in Livers of Hyperlipidemic Rats

目的:研究蓝靛果花色苷对高脂血症大鼠肝脏低密度脂蛋白受体(low density lipoprotein receptor,LDLR)、三磷酸腺苷结合盒转运体G1(ATP-binding cassette transporter G1,ABCG1)及ABCA1基因表达的影响。方法:选择2月龄雄性Wistar大鼠60只,将大鼠随机分为6组,分别为基础饲料对照组(ND,1.2 g/(kg·dm_b)生理盐水灌胃)、高脂模型对照组(HFD,1.2 g/(kg·dm_b)生理盐水灌胃)、阳性对照组(10 mg/(kg·dm_b)辛伐他汀片灌胃),蓝靛果花色苷低、中、高剂量组(HFD+L、HFD+M、HFD+H,分别给予4.0、40.0、120.0 mg/(kg·dm_b)的花色苷灌胃),持续28 d。实验结束后,测定血清总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、载脂蛋白A(apolipoprotein A,Apo-A)及载脂蛋白B(Apo-B)等血脂指标水平。取大鼠肝脏,利用实时荧光定量聚合酶链式反应测定大鼠肝脏组织中LDLR、ABCG1、ABCA1 m RNA表达量,Western blot检测LDLR蛋白表达水平。结果:蓝靛果花色苷干预后,与HFD组相比,花色苷均能不同程度地降低高血脂大鼠血清中TC、TG、LDL-C、Apo-B的含量(P<0.05或P<0.01),显著升高HDL-C及Apo-A的含量(P<0.05或P<0.01)。花色苷各剂量组LDLR蛋白和m RNA水平均增高,与HFD组比较差异有显著性(P<0.05),ABCA1 m RNA和ABCG1 m RNA的表达水平也高于HFD组,尤其是花色苷中、高剂量组差异明显(P<0.05)。结论:40.0 mg/(kg·dm_b)蓝靛果花色苷具有明显的调节血脂作用,其作用机制可能是通过上调肝脏LDLR和ABC家族基因的表达,进而调节胆固醇逆转运过程。

Objective： To investigate the effect of anthocyanins from the fruits of Lonicera caerulea（LCA） on the gene expression of low density lipoprotein receptor（LDLR）, ATP-binding cassette transporter G1（ABCG1）, and ATP-binding cassette transporter A1（ABCA1） in hyperlipidemic rat liver. Methods： A total of 60 male Wistar rats aged two months were randomly divided into 6 groups： normal diet control（ND, intragastrically administered with 1.2 g/（kg·dm_b） of physiological saline）, high-fat diet control（HFD, similarly administered with 1.2 g/（kg·dm_b） of physiological saline）, positive control（intragastrically administered with 10 mg/（kg·dm_b） of simvastatin tablets）, and low-, middle-and high-dose LCA（at 4.0, 40.0 and 120.0 mg/（kg·dm_b） groups. The administration lasted for 28 days. At the end of this period, the levels of serum total cholesterol（TC） and triglyceride（TG）, HDL cholesterol（HDL-C）, low density lipoprotein cholesterol（LDL-C）, apolipoprotein A（Apo-A） and apolipoprotein B（Apo-B） were determined. The m RNA expression levels of LDLR, ABCA1 and ABCG1 were detected by real-time polymerase chain reaction（RT-PCR） and the protein level of LDLR was evaluated by Western blot analysis. Results： Compared with the hyperlipemia model group, LCA could reduce the serum levels of TC, TG, LDL-C and Apo-B and increase the levels of HDL-C and Apo-A（P〈0.05 or P〈0.01）. The expression of LDLR protein and m RNA in all dose groups increased significantly（P〈0.05）, and the expression levels of ABCA1 and ABCG1 m RNA similarly rose; in particular, a significant increase was observed in the middle-and high-dose groups（P〈0.05）. Conclusion： 40.0 mg/（kg·dmb） Lonicera caerulea anthocyanins have a significant role in regulating blood lipids by up-regulating the expression of LDLR and ABC family genes in the liver and consequently regulating reverse cholesterol transportation in hyperlipidemic rats.