冠心康对高脂血症大鼠肝脏胆固醇稳态分子表达的动态影响

Dynamic effects of Guanxinkang on the molecule expression of hepatic cholesterol homeostasis in hyperlipidemia rats

目的观察冠心康对高脂血症大鼠肝脏胆固醇稳态分子表达的动态影响。方法 96只大鼠随机取24只作正常对照组,给予普通饲料;另72只给予高胆固醇饮食,并随机分为3组：模型组,辛伐他汀组,冠心康组。于第4、8、12周处死大鼠,采用生化法检测血脂水平,实时荧光定量PCR及Western blotting方法检测低密度脂蛋白受体（Ldlr）、1型清道夫受体（Srb1）、羟甲基戊二酰辅酶A还原酶（Hmgcr）、固醇调节元件结合蛋白2（Srebp2）基因及蛋白水平。结果与模型组比较,冠心康治疗4周、8周、12周后血清胆固醇及低密度脂蛋白有下降趋势,但差异无统计学意义（P〉0.05）。与模型组比较,冠心康可显著上调高脂血症大鼠肝脏Ldlr基因及蛋白表达水平（P〈0.05）;并于治疗4-8周和8-12周后,显著上调高脂血症大鼠肝脏Srebp2基因及蛋白表达水平（P〈0.05）,且随着时间延长表达逐渐上升。结论冠心康可动态调节高脂血症大鼠肝脏Ldlr基因及蛋白表达从而调节血脂水平,且可能通过调节Srebp2基因及蛋白水平,调节胆固醇稳态,调节血脂水平。

Objective To observe the dynamic effects of Guanxinkang on the molecule expression of hepatic cholesterol homeostasis in hyperlipidemia rats.Methods 96 SD rats were randomly divided,among which 24 rats were set as the normal control group and treated with normal diet,72 rats were treated with high cholesterol diet to induce hyperlipidemia and then randomly divided into the model group,simvastatin group,Guanxinkang group.Rats were sacrificed at 4th,8th and 12 th week.The levels of blood lipid were detected by biochemistry,the gene and protein expression levels of low-density lipoprotein receptor（Ldlr）,scavenger receptor class B type 1（Srb1）,HMG-Co A Reductase（Hmgcr） and sterol regulatory element-binding protein 2（Srebp2） were determined by real-time fluorescence quantitative PCR and Western-blot.Results Compared with the model group,the serum levels of cholesterol and low density lipoprotein were decreased after the treatment with Guanxinkang for 4 weeks,8 weeks and 12 weeks,but the difference was not statistically significant（P〉0.05）.Compared with the model group,Guanxinkang significantly up-regulated the gene and protein expression level of Ldlr in the liver of hyperlipidemia rat（P〈0.05）,and significantly up-regulated the gene and protein expression level of Srebp2 in the liver of hyperlipidemia rat after treatment for 4-8 weeks and 8-12 weeks（P〈0.05）,with a time-dependent manner.Conclusion Guanxinkang can dynamically regulate the gene and protein expression of Ldlr in the liver of hyperlipidemia rats to control the blood lipid level,and may regulate the cholesterol homeostasis by adjusting the gene and protein level of Srebp2.