高脂饲料中添加丙硫氧嘧啶对大鼠血脂、体质量及体脂的影响  

Effects of propylthiouracil addition in high fat diet on blood lipid,body weight and body fat of rats

作　　者：郝维佳[1] 杨秋实[1] 李静宜[1,2] 马毅 陆莉[1] 熊杰[1] 李宇航[1] 徐平湘[1] 陈怡[1] 薛明[1] 李晓蓉[1] Hao Weijia;Yang Qiushi;Li Jingyi;Ma Yi;Lu Li;Xiong Jie;Li Yuhang;Xu Pingxiang;Chen Yi;Xue Ming;Li Xiaorong(Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;Beijing Key Laboratory for Research on Prevention and Treatment of Tropical Disease, Beijing Friendship Hospital, Capital Medical University,, Beijing 100050, China)

机构地区：[1]首都医科大学基础医学院药理学系,北京100069 [2]首都医科大学附属北京友谊医院北京热带医学研究所热带病防治研究北京市重点实验室,北京100050

出　　处：《首都医科大学学报》2018年第3期385-392,共8页Journal of Capital Medical University

基　　金：国家自然科学基金青年基金(81202537);北京市属高等学校青年拔尖人才培育计划(CIT&TCD201404174)~~

摘　　要：目的研究添加丙硫氧嘧啶对高脂饲料诱发的高脂血症模型大鼠的血脂、体质量、体脂含量及脂肪细胞大小的影响,探讨含有丙硫氧嘧啶的高脂饲料诱发的高脂血症动物模型的适用性。方法 SD大鼠采用数字表法随机分为4组,分别为正常饲料组、正常饲料+丙硫氧嘧啶组、高脂饲料组、高脂饲料+丙硫氧嘧啶组,分别给予相应的饲料,灌胃给予丙硫氧嘧啶50 mg·kg^(-1)·d^(-1),共4周,期间记录动物的采食量、体质量、体长,检测血脂、转氨酶、甲状腺激素浓度,计算Lee's指数、肝系数、睾周脂肪和肾周脂肪系数,并进行肝脏油红O染色,脂肪组织HE染色,Image J测量脂肪细胞大小。结果添加丙硫氧嘧啶可显著升高高脂饲料诱发的动物血浆总胆固醇和低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)浓度,肝系数升高,肝脏脂质沉积,造模速度快、效果好,但是随着给予丙硫氧嘧啶时间的延长,动物采食量迅速降低,继之动物体质量、睾周脂肪质量、肾周脂肪质量、脂肪细胞面积及Lee's指数显著降低,同时伴有动物毛色发暗、缺乏光泽、活动减少及对刺激反应下降等。结论添加丙硫氧嘧啶为制作高胆固醇血症及脂肪肝模型的有效方法,但是在血浆总胆固醇和LDL-C浓度升高、肝脏脂肪沉积的同时,动物体质量明显下降,体脂减少,脂肪细胞面积减小的特点与临床常见的饮食相关的高血脂特征不符,并且丙硫氧嘧啶对多种脂代谢酶有影响,进行降脂药物机制研究时可能会影响对药物作用靶点的分析,因此进行降胆固醇药物药效学研究可适当选用,进行药物机制研究时需根据研究目的慎重选用。Objective To investigate the effects of propylthiouracil on the body weight,body fat content and adipocyte size in hyperlipidemic rats induced by high-fat diets,and to investigate the applicability of the hyperlipidemia animal model induced by high fat diet containing propylthiouracil. Methods The SD rats were divided into 4 groups： normal diet,normal diet ＋ propylthiouracil,high fat diet and high fat diet ＋ propylthiouracil group,and were given the corresponding feed,and were given propylthiouracil 50 mg·kg^-1·d^-1 by gavage. The animals＇ feed intake,body weight,blood lipid,thyroid hormone levels were measured,and the Lee＇s index,liver index,perirenal adipose index,and epididymal adipose index were calculated. Oil red staining of liver tissue and HE staining of epididymal fat were made. Results Addition of propylthiouracil significantly increased lipid levels in animals given high-fat diet,with faster modeling speed and higher serum cholesterol level and low density lipoprotein-cholesterol（ LDL-C）,and liver lipid deposition. However,with prolonged intake of propylthiouracil,animal feed intake rapidly decreased,followed by animal body weight,perirenal fat and epididymal fat weight,adipocyte area,and Lee＇s index. At the same time,the animals showed dry and yellow hair,activity reduction,lags in response.Conclusion The addition of propylthiouracil is an effective method of making a model of hypercholesterolemia but with a significant reduction in body weight,body fat,and size of adipocyte. These characteristics were not consistent with the characteristics of common hyperlipidemia associated with high-fat diet in clinical practice. So addition of propylthiouracil is an effective method to mimic hypercholesterolemia associated with hypothyroidism,but it is not appropriate to characterize other types of hyperlipidemia. On the other hand,propylthiouracil has impact on a variety of lipid metabolism enzymes,may interfere with the correct judgment of drug＇s targets when doing a study on drug＇s lipid-

关 键 词：丙硫氧嘧啶 高脂饲料 高脂血症 体质量 体脂 Lee's指数 

分 类 号：R965[医药卫生—药理学]