饮食干预建立2种非酒精性脂肪性肝病小鼠模型比较  

Comparison of mouse models of nonalcoholic fatty liver disease established by two dietary interventions

作　　者：刘金存 许源慧 亓照耀 孙红光 齐鑫鑫[1] 从美丽 刘涛[1] LIU Jin-cun;XU Yuan-hui;QI Zhao-yao;SUN Hong-guang;QI Xin-xin;CONG Mei-li;LIU Tao(School of Public Health,Xinjiang Medical University,Urumqi,Xinjiang 830011,China)

机构地区：[1]新疆医科大学公共卫生学院,新疆乌鲁木齐830011

出　　处：《毒理学杂志》2025年第1期45-53,72,共10页Journal of Toxicology

基　　金：新疆维吾尔自治区自然科学基金重点项目(2022D01D36)。

摘　　要：目的利用高脂高糖饮食(High-fat and high-sugar diet,HFHS)和低蛋氨酸胆碱缺乏高脂饮食(methionine and choline-free high-fat diet,MCD)建立C57BL/6小鼠非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)模型,探究2种模型的疾病进展情况,为模型应用提供参考。方法将64只C57BL/6雄鼠,随机分为8组,每组8只。HFHS模型给予高脂饲料和20%果糖饮水,包括4个组:HFHS正常组、HFHS 3周组、HFHS 9W组和HFHS 14W组;MCD模型给予低蛋氨酸和胆碱缺乏高脂饲料,正常饮水,包括4个组:MCD正常组,MCD 3W组,MCD 9W组和MCD 14W组;2种模型正常组均给予普通饲料和正常饮水。分别在3、9和14周处死对应模型组和正常组小鼠,测量血糖及血清AST、ALT、TG、TC、LDL-C和HDL-C水平。取肝组织行苏木素-伊红(HE)和油红O染色。结果MCD模型组:与MCD正常组比较,MCD模型各组之间血糖值无差异;MCD 3W组和MCD 14W组AST和ALT明显升高(AST:F=26.33,ALT:F=95.74,P<0.001),MCD 9W组AST/ALT值升高(F=7.64,P<0.01),MCD 9W组TC升高(F=12.33,P<0.001);肝病理结果显示,MCD模型组肝细胞数量减少,细胞质内出现大量脂质,有炎性细胞浸润现象。HFHS模型组:与HFHS正常组比较,HFHS 9W组和HFHS 14W组血糖值升高(F=6.52,P<0.01),HFHS模型组AST、ALT及AST/ALT值各组间差异均无统计学意义,HFHS模型组各组TC值均升高(F=20.47,P<0.001),而TG各组之间差异无统计学意义,HFHS 3W组和HFHS 14W组LDL-C升高(F=6.70,P<0.01),HFHS模型组门静脉周围仅出现少量脂质。结论2种饲料方案均可建立小鼠NAFLD模型,二者的主要区别是疾病进展速度和肝脂肪变性程度,MCD模型病程进展较快,肝病变严重;HFHS模型进展缓慢,肝病理改变较轻。Objective To establish a model of nonalcoholic fatty liver disease(NAFLD)in C57BL/6 mice by using high-fat and high-sugar diet and high-fat diet(HFHS)and methionine and choline-free high-fat diet(MCD),to explore the disease progress to provide reference for the application of the model.Methods Sixty-four C57BL/6 male rats were randomly divided into eight groups,each group has eight animals.HFHS model was given high-fat feed and 20%fructose drinking water,including four groups:HFHS normal group,HFHS 3W group,HFHS 9W group and HFHS 14W group;The MCD model was given high-fat diet with low methionine and choline deficiency and normal drinking water,including four groups:MCD normal group,MCD 3W group,MCD 9W group and MCD 14W group;The normal group was given ordinary feed and normal drinking water.The mice in the corresponding group were killed at 3 weeks,9 weeks and 14 weeks respectively,and the blood sugar and serum levels of AST,ALT,TG,TC,LDL-C and HDL-C were measured.Liver tissue was stained with HE and Oil red O.Results MCD model:Compared with MCD normal group,there was no difference in blood sugar value between each group in MCD model;AST and ALT in MCD 3W group and MCD 14W group were significantly increased(AST:F=26.33,ALT:F=95.74,P<0.001),AST/ALT value in MCD 9W group was increased(F=7.64,P<0.01),and TC in MCD 9W group was increased(F=12.33,P<0.001).In MCD model group,the number of hepatocytes decreased,a large number of lipids appeared in cytoplasm,and there was inflammatory infiltration.HFHS model:Compared with HFHS normal group,the blood glucose values in HFHS 9W group and HFHS 14W group increased(F=6.52,P<0.01),and there was no statistical difference in AST,ALT and AST/ALT values among HFHS model groups.TC values in HFHS model group all increased(F=20.47,P<0.001),but there was no statistical difference among TG.LDL-C in HFHS 3W group and HFHS 14W group increased(F=6.70,P<0.01),and only a small amount of lipid appeared around portal vein in HFHS model group.Conclusion NAFLD models of different degrees can be

关 键 词：非酒精性脂肪性肝病 高脂高糖饮食 低蛋氨酸和胆碱缺乏高脂饮食 

分 类 号：R99[医药卫生—毒理学] R114[医药卫生—药学]