大黄酸对合并非酒精性脂肪性肝炎的HBV转基因小鼠肝病恶化的防治作用  

Protective effects of rhein on hepatic progression in HBV-transgenic mice with nonalcoholic steatohepatitis induced by a high-fat diet

作　　者：卞冬雪[1] 刘静[1] 陆璐 刘红 过建春 杨文君[3] 柳银兰[3] 罗燕[3] 庄振杰[3] 陈建玉 施军平[3] 荀运浩 

机构地区：[1]浙江中医药大学,310053 [2]浙江省东阳市中医院消化科 [3]杭州师范大学转化医学平台杭州师范大学附属医院 [4]杭州市西溪医院肝病科

出　　处：《中华实验和临床病毒学杂志》2013年第5期328-331,共4页Chinese Journal of Experimental and Clinical Virology

基　　金：浙江省自然科学基金项目（Y2091159,Y2091200）;国家自然科学基金项目（81070316）

摘　　要：目的探讨大黄酸对合并肝脂肪变的HBV转基因小鼠肝病恶化的防治作用。方法4周龄HBV转基因小鼠130只，高脂饲料喂养16周建立慢性HBV携带合并肝脂肪变小鼠模型；之后随机分为对照组（恢复正常饮食）、模型组（继续高脂饮食）、大黄酸组[120g／（kg·d）灌胃]、易善复组[69．2g／（kg·d）灌胃]4组，每组30只，第24和48周末每组分别处死15只，采集血清全自动生化仪检测ALT、AST、总胆固醇（Tc）、甘油三酯（TG）、空腹血糖（FPG），荧光定量PCR法测定HBV．DNA，肝组织常规HE染色观察组织学变化。结果①高脂喂养48周后小鼠肝组织可见脂肪变、小叶内淋巴细胞浸润和肝细胞气球样变，NAFLD肝组织活动度计分（NAS）接近NASH（3．58±1．44）。②肝组织光镜观察示24和48周末模型组NAS高于对照组，大黄酸组NAS无下降，易善复组48周末NAS降低。③血生化示24周时各组间TC、TG、FPG差异明显，大黄酸与易善复组均见增高的TC、TG、FPG水平下降；48周末组间TC、FPG仍保持原差异趋势。④24及48周末各组间血清HBV载量均差异明显（P〈0．05），模型组与对照组水平相似，大黄酸组变化不明显，易善复组明显低于模型组。结论高脂配方喂养HBV转基因小鼠可建立慢性HBV携带合并NASH小鼠模型，大黄酸可一定程度改善该模型的糖脂代谢，但对肝组织病变作用有限。回复正常饮食的组织学干预效应最佳。Objective To investigate the beneficial effects of Rhein （RH） on hepatic progression in hepatitis B virus （HBV） -transgenic mice with nonalcoholic steatohepatitis induced by a high-fat （HF） diet. Methods A mice modelof BV chronic infection concomitant with liver steatosis was induced by a HF diet in 4-week old HBV-transgenic mice for 16 weeks （n = 130）. Thereafter, the mice were divided randomly into control group （back to normal chow）, model group （continuing HF diet）, RH group [continuing HF diet and administering with 120 rag/（ kg. d） RH by gavage] and Essentiale group [ continuing HF diet and administering with 69.2 rag/（kg.d） Essentiale by garage] with 30 mice in each, and were sacrificed at the end of 24-week and 48-week respectively. Serum levels of alanine aminotransferase （ ALT）, aspartate aminotransferase （ AST）, total cholesterol （ TC）, triglyceride （TG） and fasting plasma glucose （FPG） were measured by an automatic biochemical analyzer, and serum HBV-DNA was determined with qPCR. Hepatic histology was evaluated by HE staining with a light microscope. Results （1）An histological change composed of steatosis, lymphocytes intralobular infiltration and ballooning was observed after 48 weeks feeding of HF diet, in part mimicking that of NASH patients as evidenced by a NAFLDactivity score （NAS） of 3.58 ＋ 1.44 points. Histologically, the NAS of model group was higher than that of control group at both time points. RH failed to lessen NAS whereas Essentiale improved the NAS at 48- week. （3）Serum levels of TC, TG and FPG were significantly different between 4 groups at 24-week, with a comparable low value in both RH and Essentiale group. A similar change was evident at 48-week. （4）In terms of HBV viral load, a significantly lower level in Essentiale group than the others was observed at both time points. Conclusion HF diet feeding is able to induce a mouse model of HBV chronic infection concomitant with NASH. RH is effective in alleviating th

关 键 词：大黄酸 脂肪肝 肝炎病毒 乙型 转基因小鼠 

分 类 号：R259[医药卫生—中西医结合]