豚鼠高脂血症模型的建立及机制探讨

目的建立豚鼠高脂血症模型,探讨模型形成机制并与大鼠模型进行比较。方法豚鼠模型和大鼠模型1组用低胆固醇（0.1%）饲料诱导,大鼠模型2组用高胆固醇（1%）饲料诱导,连续诱导4周。第3、4周分别取血测定血清脂质水平及CETP表达,4周末剖取肝脏检测肝脏FC、TG、ACAT、CYP7A1等指标。动态观察两种动物形成高脂血症状况。结果与对照组比较,豚鼠模型组于第3周血清TC、LDL-C、TG分别升高3.92倍、3.75倍和1.24倍,4周末血清CETP表达、肝脏ACAT活性明显增加,但肝CYP7A1水平变化不大。大鼠模型1组经低胆固醇饲料诱导4周,血脂水平变化不明显,模型2组经高胆固醇饲料诱导于第3周血清TC、LDL-C分别升高1.24倍和1.54倍,明显低于同期豚鼠模型组,4周末大鼠两个模型组肝CYP7A1活性显著增强,血清TG、CETP水平、肝ACAT活性均未见明显变化。结论豚鼠对高脂饲料较大鼠敏感,是一种比大鼠更理想的高血脂模型动物,模型形成机制与血清CETP表达、肝ACAT及CYP7A1活性变化密切相关。

Establishment and Mechanisms of a Guinea Pig Model of Hyperlipidemia and Comparison with the Rat Model

Objective To establish a guinea pig model of hyperlipidemia,investigate its mechanism,and compare it with rat model.Methods Diet with low cholesterol（0.1%） was given to the guinea pig model group and rat model group 1.Diet with high cholesterol（1%） was given to the rat model group 2.Serum lipid concentrations of both animals were measured at the end of third and fourth weeks.After 4 weeks,the concentration of serum CETP and hepatic lipids,activities of hepatic ACAT and CYP7A1 were measured.Results Compared with the control group,the guinea pig serum TC,LDL-C and TG stepped up to 3.92 times,3.75 times and 1.24 times,respectively,after 3 weeks and were kept up to the fourth week.After 4 weeks,the concentration of serum CETP and activity of hepatic ACAT reached a stable high level,while CYP7A1 activity changed little.Serum lipids in rat model group 1 were not changed within 4 weeks.In the rat model group 2,serum TC and LDL-C stepped up to 1.24 times and 1.54 times after 3 weeks,respectively.At the end of the fourth week,hepatic CYP7A1 activity reached a significantly high level in both of the rat model groups,however,serum TG,CETP concentration and hepatic ACAT activity were not changed significantly.Conclusion Guinea pigs are more sensitive than rats to the high-fat diet,and it can be used to set up a hyperlipidemia model with low cholesterol in a short period.So guinea pigs are more suitable to be used to establish a hyperlipidemia model.The changes of serum CETP concentration,hepatic ACAT and CYP7A1 activities are closely related to the mechanisms of hyperlipidemia development.