新型高脂血症易感(WSHc)大鼠非酒精性脂肪肝病模型的建立与病理特点研究  

Establishment and pathological characteristics of a non-alcoholic fatty liver disease model in a new type of hyperlipidemia-susceptible(WSHc)rats

作　　者：马全鑫[1] 张利棕[1] 戎亦骊 何蒙娜 郁晨 蔡月琴[1] 陈民利[1] MA Quanxin;ZHANG Lizong;RONG Yili;HE Mengna;YU Chen;CAI Yueqin;CHEN Minli(Animal Experimental Research Center/Institute of Comparative Medicine,Zhejiang Chinese Medical University,Hangzhou 310053,China;Department of Ultrasound Medicine,the First Affiliated Hospital of Zhejiang University,Hangzhou 310003)

机构地区：[1]浙江中医药大学,动物实验研究中心/比较医学研究所,杭州310053 [2]浙江大学医学院附属第一医院,超声医学科,杭州310003

出　　处：《中国实验动物学报》2020年第3期314-322,共9页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家卫生计生委科学研究基金-浙江省医药卫生重大科技计划项目(2016149056);浙江省自然基金(LQ20H180013)。

摘　　要：目的利用一种新型的高脂血症易感(WSHc)大鼠建立非酒精性脂肪肝病(NAFLD)模型,观察其血液生化指标变化及病理特点,探讨其应用与科研价值,为NAFLD疾病动物模型提供新的选择。方法 20只7~8周龄的WSHc大鼠,随机平均分为2组,分别饲喂普通饲料和高脂饲料;另取20只同周龄的Wistar大鼠,采取相同处理方式分组作为品系对照。持续饲喂12周后,检测血清TC、TG、ALT和AST水平,并进行弹性超声成像。处死动物后取肝进行HE、油红O、Masson和免疫荧光染色,观察各组大鼠肝大体细胞形态、脂质沉积、炎症反应和纤维化情况,分析高脂饲喂后WSHc大鼠肝的病变特点。结果与饲喂高脂饲料的Wistar大鼠比较,WSHc大鼠经高脂诱导后,血清总胆固醇显著升高并与临床高脂血症患者接近;肝脂质异常沉积并形成大泡性脂滴;脂滴周围有炎症细胞浸润形成炎症灶,巨噬细胞增多;可见散在的纤维化病变。然而,这些病理变化在高脂诱导的Wistar大鼠肝组织中并未发现。结论相较于Wistar大鼠,WSHc大鼠高脂诱导后血脂与肝酶接近临床水平,肝组织中有更严重的脂质沉积和炎症反应,且伴有散在的肝纤维化,因此可作为一种新的、理想的NAFLD动物模型。Objective To establish a non-alcoholic fatty liver disease(NAFLD)rat model in a new type of hyperlipidemia(WSHc)rat.We observed the pathological characteristics of the NAFLD model and explored possible research applications,as well as new options for animal models of NAFLD.Methods 20 WSHc rats aged 7–8 weeks were randomly divided into 2 groups according to whether they would receive a common diet or high-fat diet.Another 20 Wistar rats of the same age were then grouped as a strain control,and received the same treatment.After 12 weeks of continuous feeding,blood samples were taken to detect blood biochemical indicators and elastic ultrasound imaging was performed.After execution of the animals,the liver tissue was subjected to HE,oil red“O”,Masson,and immunofluorescent staining,and the general cell morphology,lipid performance,inflammatory response,and liver fibrosis stage in each group were observed.The lesion characteristics of the liver of WSHc rats after a high-fat diet were analyzed.Results Compared with Wistar rats on a high-fat diet,WSHc rats showed a significant increase in serum total cholesterol,similar to that seen in patients with clinical hyperlipidemia.We also found that liver lipids were abnormally deposited to form lipid droplets,and that inflammatory cells positioned around the lipid droplets formed an inflammatory lesion.Further,we observed an increase in macrophages and instances of scattered fibrosis.These pathological changes were not found in the liver tissue of high-fat-exposed Wistar rats.Conclusions Compared with conventional rats,WSHc rats on a high-fat diet represent a more clinically similar NAFLD animal model,which is characterized by blood biochemical indicators,a severe inflammatory response,and sporadic liver fibrosis approaching clinical levels.

关 键 词：高脂血症易感大鼠 WSHc大鼠 非酒精性脂肪肝病 动物模型 

分 类 号：Q95-33[生物学—动物学]