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

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·d mb） 生理盐水灌胃）、高脂模型对照组（HFD，1.2 g/（kg·d mb）生理盐水灌胃）、阳性对照组（10 mg/（kg·d mb） 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·d mb）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 mRNA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mRNA水平均增 高，与HFD组比较差异有显著性（P＜0.05），ABCA1 mRNA和ABCG1 mRNA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·d mb）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。

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

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·d mb) of physiological saline), high-fat diet control (HFD, similarly administered with 1.2 g/(kg·d mb) of physiological saline), positive control (intragastrically administered with 10 mg/(kg·d mb) of simvastatin tablets), and low-, middle- and high-dose LCA (at 4.0, 40.0 and 120.0 mg/(kg·d mb) 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 mRNA 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 mRNA in all dose groups increased significantly (P < 0.05), and the expression levels of ABCA1 and ABCG1 mRNA similarly rose; in particular, a significant increase was observed in the middle- and high-dose groups (P < 0.05). Conclusion: 40.0 mg/(kg·d mb) 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.