高脂血症食蟹猴模型的建立及初步分析

Establishment and preliminary analysis of a hyperlipidemic cynomolgus monkey model

目的建立与人类疾病特征相似的高血脂食蟹猴模型,为降脂药(特别是生物类降脂药)的研发提供理想的动物模型。方法将优化、定型的半流质高糖高脂膳食乳剂,每周6 d经鼻饲灌喂给药处理组雄性食蟹猴,定期监测猴体重(BW)、体重质量指数(BMI)、血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)等指标,对其血脂指标的变化趋势进行分析。结果与相应的对照组相比,至造模第3个月,处理组6只中老年雄性食蟹猴和5只成年雄性食蟹猴全部造模成功,至造模第21个月所有处理组雄性食蟹猴依然维持在较高血脂水平。结论连续3个月定量灌喂半流质高糖高脂膳食乳剂可成功制备高脂血症食蟹猴模型,该模型具有高胆固醇血症和高低密度脂蛋白胆固醇血症的特征,可用于高脂血症发病机理研究及药物临床前药效评价研究。

Objective To establish a hyperlipidemic cynomolgus monkey model with human disease characteristics,and to provide an ideal animal model for the development of lipid-lowering drugs,especially lipid-lowering biopharmaceuticals.Methods The male cynomolgus monkeys in different treatment groups were gavaged with a formulated semi-liquid high fat/high sugar dietary emulsion 6 days per week.Body weight(BW),body mass index(BMI),serum total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),and other indexes were monitored regularly,and changes in the blood lipid profiles were analyzed.Results Compared with the corresponding control group,by the third month of modeling,all six middle-aged and old male cynomolgus monkeys and five adult male cynomolgus monkeys in the treatment group were successfully modeled.By the 21st month,all male cynomolgus monkeys in the treatment group still maintained a relatively high level of blood lipid.Conclusions A hyperlipidemic cynomolgus monkey model is successfully created through quantitative gavage using a high sugar and high fat dietary emulsion for 3 months.The model demonstrates the characteristics of hypercholesterolemia and high-density lipoprotein cholesterolemia,and it can be used to study the pathogenesis of hyperlipidemia and for pre-clinical drug evaluations of pharmacodynamics.