山楂及山楂黄酮预防大鼠脂质代谢紊乱的分子机制研究

MOLECULAR MECHANISM OF HAWTHORN AND ITS FLAVONOIDS IN PREVENTION ON LIPID METABOLISM DISORDER IN RATS

目的 探讨山楂及山楂黄酮调节大鼠脂质代谢紊乱的效果分子机制。方法 在建立大鼠高脂血症模型基础上 ,观察山楂及山楂黄酮对大鼠血脂水平、抗氧化能力、肝脏低密度脂蛋白受体 (LDLR)的 m RNA和蛋白水平及功能等方面的影响。结果 山楂及山楂黄酮能显著抑制喂高脂高胆固醇饲料大鼠血清总胆固醇 (TC)、低密度脂蛋白 -胆固醇 (LDL- C)和 Apo B浓度 ,显著升高高密度脂蛋白 -胆固醇 (HDL- C)和 Apo Al浓度 ,但对甘油三酯 (TG)影响不大。山楂及山楂黄酮还能显著降低血清和肝脏丙二醛 (MDA)含量 ,增强红细胞和肝脏超氧化物歧化酶 (SOD)的活性 ,同时增强全血谷胱甘肽还原酶 (GSH- Px)活性。逆转录聚合酶链反应 (RT- PCR)实验显示高脂高胆固醇饲料能显著降低大鼠肝脏 LDLR m RNA水平 ,山楂及山楂黄酮能显著升高大鼠肝脏LDLR m RNA水平。 Western印迹实验结果表明 ,高脂高胆固醇饲料能显著降低大鼠肝脏低密度脂蛋白受体蛋白水平 ,山楂及山楂黄酮能显著增加大鼠肝脏 LDLR的蛋白水平。放射性配体结合力试验表明 ,山楂及山楂黄酮显著增加了大鼠肝脏 LDLR数目 ,而对亲和力影响不明显。结论 山楂及山楂黄酮主要通过调节大鼠肝脏 LDLR转录水平和提高抗氧化能力抑制脂质过氧化物预防脂质代谢紊乱。

Objective: To elucidate the molecular mechanism of haw and its flavonoids in prevention on lipid metabolism disorders in rats. Methods: On the basis of establishing hyperlipidemia rat model,blood lipids,antioxidative capacity,hepatic LDLR mRNA and protein levels, were investigated after 8 week feeding of atherogenic diet. [WT5FZ]Results:[WT5BZ] Both haw and its flavonoids significantly reduced the serum TC,LDL C,ApoB concentration and improved atherosclerotic indices,increased the HDL C and ApoA l levels, but have no significant effects on weight,serum TG level,perirenal and peritesticular fat content of rats. They significantly decreased MDA content in both serum and liver,increased RBC and hepatic SOD activities and promoted the activity of GSH Px as well.The results of RT PCR and Western blot test showed that high fat and high cholesterol feeding could significantly induce the reduction of LDLR mRNA and protein levels,while haw and its flavonoids could increase LDLR mRNA and protein levels parallelly.The radioreceptor binding assay showed that haw and flavonoids could increase hepatic LDLR density,but could not change the affinity of LDL to hepatic membrane LDLR. Conclusion: Haw and its flavonoids prevent lipid metabolism disorders through upregulation of LDLR transcription level and increase of antioxidative capacity.