Lieber-DeCarli液体饲料中三种方法诱导酒精性肝病小鼠模型的比较

Comparison of three methods for inducing alcoholic liver disease in mice models using Lieber-DeCarli liquid diet

目的配制Lieber-DeCarli液体饲料,通过酒精热量过渡、酒精不过渡、酒精体积过渡三种方法诱导酒精性肝病(alcoholic liver disease,ALD)小鼠模型,比较其肝功能损伤程度、血脂水平和肝脏脂肪变性程度。方法健康雄性C57BL/6J小鼠36只,随机分为6组(n=6),即酒精热量过渡对照组(A1)、酒精热量过渡组(A2)、酒精不过渡对照组(B1)、酒精不过渡组(B2)、酒精体积过渡对照组(C1)、酒精体积过渡组(C2),在饲喂相应液体饲料的第16、22、28 d分别处死对应组小鼠,测定并比较血清天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、谷氨酸氨基转移酶(glutamic acid aminotransferase,ALT)、总胆固醇(total cholesterol,TC)、甘油三酯(triglycerides,TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)含量;肝脏苏木精-伊红染色(H&E染色)观察肝脏病理改变;肝脏油红O染色观察肝脏脂肪变性。结果血清生化结果显示,各模型组小鼠血清ALT、AST、TG含量均高于其对照组(P<0.05);A2、B2、C2组小鼠血清AST、ALT含量无明显差异(P>0.05);A2组小鼠血清TC、HDL-C含量高于B2、C2组(P<0.05);A2、C2组小鼠血清LDL-C含量均高于B2组(P<0.05)。病理结果显示,各模型组小鼠肝脏H&E染色均可见肝细胞脂肪变性;肝脏油红O染色均可见橘红色或红色脂滴聚集。结论Lieber-DeCarli液体饲料中三种方法诱导的ALD小鼠模型肝功能损伤无差异,表现为不同程度的肝脏脂肪变性及血脂异常。

Objective Prepare Lieber-DeCarli liquid feed and induce an alcoholic liver disease(ALD)mouse model using three methods:alcohol calorie transition,alcohol non transition,and alcohol volume transition.Compare the extent of liver function damage,blood lipid levels,and liver steatosis among the different groups.Method A total of 36 healthy male C57BL/6J mice were randomly divided into 6 groups(n=6):the alcohol calorie transition control group(A1),the alcohol calorie transition group(A2),the alcohol non transition control group(B1),the alcohol non transition group(B2),the alcohol volume transition control group(C1),and the alcohol volume transition group(C2).Each group of mice was fed the corresponding liquid diet.On the 16th,22nd,and 28th days,mice from the corresponding groups were euthanized,and the levels of serum aspartate aminotransferase(AST),glutamic acid aminotransferase(ALT),total cholesterol(TC),triglycerides(TG),high density lipoprotein cholesterol(HDL-C),and low density lipoprotein cholesterol(LDL-C)were measured and compared.H&E staining of the liver was used to observe pathological changes,while Oil Red O staining was used to observe hepatic steatosis.Results The serum biochemical results showed that the levels of ALT,AST,and TG in the serum of mice in each model group were higher than those in their respective control groups(P<0.05).There was no significant difference in serum AST and ALT levels between the A2,B2,and C2 groups(P>0.05).The serum TC and HDL-C levels in group A2 mice were higher than those in groups B2 and C2(P<0.05),while the serum LDL-C levels in groups A2 and C2 mice were higher than those in group B2(P<0.05).The pathological examination results showed that hepatic steatosis was observed by H&E staining,and orange-red or red lipid droplets were observed by Oil Red O staining in the liver of all model groups.Conclusion There was no difference in liver function damage induced by the three methods using Lieber DeCarli liquid feed for alcoholic liver disease mouse models,but different degrees of liver steatosis and lipid abnormalities could occur.