慢性乙型肝炎病毒携带合并非酒精性脂肪性肝病小鼠模型建立与观察  

Model building-up and observation on the mouse carried chronic hepatitis B and nonalcoholic fatty liver disease

作　　者：陆璐 柳银兰[2] 杨文君[2] 刘静[3] 罗燕[2] 庄振杰[2] 陈建玉[2] 卞冬雪[3] 荀运浩 施军平[2] 

机构地区：[1]浙江省东阳市中医院,322100 [2]杭州师范大学附属医院 [3]浙江中医药大学 [4]杭州市西溪医院

出　　处：《中华实验和临床病毒学杂志》2013年第5期332-335,共4页Chinese Journal of Experimental and Clinical Virology

基　　金：浙江省自然科学基金（项目编号Y2091200,Y2091159）

摘　　要：目的建立慢性乙型肝炎病毒（HBV）携带合并非酒精性脂肪性肝病（NAFLD）小鼠模型。方法4周龄BALB／cHBV转基因小鼠100只，雌雄各半，高脂组70只予高脂饲料喂养，正常组30只予普通饲料喂养。16周末随机处死高脂组小鼠10只，肝组织及血清学检测确认目标模型建立。造模成功后高脂组再随机分为模型组和对照组，每组30只，模型组继以高脂饲料喂养，对照组改以普通饲料喂养，正常组维持原普通喂饲，连续72周（含造模16周）。第24、48和72周末每组分别随机处死小鼠10只，全自动生化仪检测血清ALT、AST、TC、TG、FBG，荧光定量PCR法检测HBV—DNA，化学发光法检测HBsAg，肝组织切片后HE染色评价组织学变化，观察小鼠模型的动态演变情况。结果①高脂饲料喂养16周后，小鼠体质量增加，血清ALT、AST、TC、TG、FBG等各项生化指标升高，HBV．DNA阳性，肝组织HE染色示肝细胞明显大泡性脂肪变性和小叶内淋巴细胞浸润，NAFLD活动度评分（NAS）接近NASH，慢性HBV携带合并NAFLD小鼠模型建立成功。②模型组血清TC和TG值在各观察点均高于对照组和正常组。③24周和72周各组间HBV—DNA值存在明显差异，且差异具有统计学意义（P〈0．05）。④48周和72周各组间NAS存在明显差异，且差异具有统计学意义（P〈0．05）。结论①高脂喂养HBV转基因小鼠可建立慢性HBV携带合并NAFLD小鼠模型。②NAFLD在一定程度上促进HBV携带小鼠的肝病进展。Objective Establish the model of mouse with chronic hepatitis B virus （HBV） and nonalcoholic fatty liver disease （NAFLD）. Methods Take 100 HBV transgenic, BALB/c mice of 4 weeks old, with each gender half. Then pick out 70 mice in one group to feed high-fat feed and the rest to feed normal feed. At the end of week 16, random kill 10 mice of high-fat, then liver tissue and serological detection target identification model is established in this paper. After that, divide the mice into model group and comparison group with 30 mice in each group. Feed model group with high-fat feed, comparison group with normal feed and normal group with normal feed till week 72 （including previous 16 weeks）. Kill 10 mice of each group at the end of week 24, 48 and 72 respectively, fully automatic biochemical instrument detection of serum ALT, AST, TC, TG, FBG, fluorescence quantitative PCR method to detect HBV-DNA, chemiluminescence detection of HBsAg, liver biopsy after HE staining to evaluate histology change, observe mice model of dynamic evolution. Results Feed high fat feed after 16 weeks, mice＇s weight, serum ALT, AST, TC, TG, FBG and blood biochemical indicators increased, HBV-DNA positive, liver HE staining obviously big blister fatty degeneration of liver cells and within the lobule lymphocytes infiltration,NAFLD activity score （NAS） getting close to NASH, the model of chronic HBV carries with NAFLD mouse built successfully. The TC and TG values of model group in each period were higher than that of comparison group and normal group. In week 24 and 72, HBV-DNA values of each group are obvious different from the other two groups and the difference can be applied to statistical significance （ P 〈 0. 05 ）.In week 48 and 72, NAS of each group are obvious different from the other two groups and the difference can be applied to statistical significance （ P 〈 0. 05 ）. Conclusions Chronic HBV carries with NAFLD mice model can be established by HBV transgenic mice fed by high fat feed. NAFLD accelerate

关 键 词：脂肪肝 肝炎病毒 乙型 转基因小鼠 

分 类 号：R512.62[医药卫生—内科学]