CAJ | 학술논문

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[120 g/(kg·d)灌胃]、易善复组[69.2 g/(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.
목적 탐토대황산대합병간지방변적HBV전기인소서간병악화적방치작용.방법 4주령HBV전기인소서130지,고지사료위양16주건립만성HBV휴대합병간지방변소서모형；지후수궤분위대조조(회복정상음식)、모형조(계속고지음식)、대황산조[120 g/(kg·d)관위]、역선복조[69.2 g/(kg·d)관위]4조,매조30지,제24화48주말매조분별처사15지,채집혈청전자동생화의검측ALT、AST、총담고순(TC)、감유삼지(TG)、공복혈당(FPG),형광정량PCR법측정HBV-DNA,간조직상규HE염색관찰조직학변화.결과 ①고지위양48주후소서간조직가견지방변、소협내림파세포침윤화간세포기구양변,NAFLD간조직활동도계분(NAS)접근NASH(3.58±1.44).②간조직광경관찰시24화48주말모형조NAS고우대조조,대황산조NAS무하강,역선복조48주말NAS강저.③혈생화시24주시각조간TC、TG、FPG차이명현,대황산여역선복조균견증고적TC、TG、FPG수평하강；48주말조간TC、FPG잉보지원차이추세.④24급48주말각조간혈청HBV재량균차이명현(P＜0.05),모형조여대조조수평상사,대황산조변화불명현,역선복조명현저우모형조.결론 고지배방위양HBV전기인소서가건립만성HBV휴대합병NASH소서모형,대황산가일정정도개선해모형적당지대사,단대간조직병변작용유한,회복정상음식적조직학간예효응최가.
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 model of HBV 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 mg/(kg· d) RH by gavage] and Essentiale group [continuing HF diet and administering with 69.2 mg/(kg·d) Essentiale by gavage] 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 ①An 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 NAFLD activity score (NAS) of 3.58 ± 1.44 points.②Histologically,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.③Serum 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.④In 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 the glucose and lipid metabolism but ineffective in improving the hepatic histology in this model,in contrast,backing to normal chow achieved a better effect in this aspect.