依折麦布对非酒精性脂肪肝模型金黄地鼠血清生化指标的影响

Effect of Ezetimibe on Serum Metabolites in High-Fat-Diet Fed Hamsters with Nonalcoholic Fatty Liver Disease

目的采用氢质子磁共振波谱(1H-MRS)和磁共振成像(MRI)技术构建金黄地鼠非酒精性脂肪肝的药效学评价体系,并初步评价依折麦布对高脂膳食诱导的金黄地鼠非酒精性脂肪肝病模型的影响。方法将30只雄性金黄地鼠随机分为正常对照组、模型对照组和依折麦布组,每组10只。正常对照组给予正常饲料,模型对照组和依折麦布组给予高脂饲料,2周后依折麦布组开始灌胃依折麦布2.7 mg·kg^(-1)·d^(-1)。给药第12周时,采用德国布鲁克7.0T小动物MRI检查肝脏和内脏脂肪含量,并对肝组织进行病理学分析。处死前收集金黄地鼠血清,检测血清中血脂和转氨酶水平。结果与正常对照组比较,模型对照组金黄地鼠肾周及腹股沟脂肪显著增加;依折麦布组动物肝脏组织中未出现脂滴空泡,肾周及腹股沟脂肪减少。正常对照组肝脏脂质子峰强度与水质子峰强度比值(MWR)为17.64±8.97,模型对照组为270.28±110.44,依折麦布组为57.19±27.49,差异有统计学意义(P<0.01)。正常对照组多不饱和指数(PUI)为0.035±0.023,模型对照组为0.007 2±0.005 3,依折麦布组为0.024±0.019,差异有统计学意义(P<0.01);与正常对照组比较,模型对照组血清三酰甘油(TG)、总胆固醇(TC)、游离脂肪酸(FFA)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平显著升高(P<0.01);与模型对照组比较,依折麦布组血清TG、TC、FFA、LDLC、ALT和AST含量显著降低(P<0.01)。结论1H-MRS和MRI技术可应用于构建金黄地鼠非酒精性脂防肝的药效学评价体系,依折麦布对高脂膳食诱导的金黄地鼠非酒精性脂肪肝有显著的改善作用。

Objective To construct the evaluation system of nonalcoholic fatty liver disease in hamsters using 7. 0 T -1H-MRS and MRI and apply it to evaluation of effect of ezetimibe on nonalcoholic fatty liver disease in hamsters. Methods Thirty male hamsters were randomly divided into three groups,normal control group,model control group and ezetimibe group.Normal control group was given chow diet,model control group and ezetimibe group was given high fat diet（ HFD）. Two weeks later,the ezetimibe group was administrated with ezetimibeat 2.7 mg·kg-（-1）·d-（-1）.After the 12 weeks of ezebimibe treatment,the MRI examinations were done on a 7T Bruker Biospec imaging system equipped with a 40 cm horizontal bore magnet. Then the hamsters were sacrificed to collect serum for chemistry analysis and livers for histopathologic examination. Results Compared with normal control group,the perirenal and inguinal adipose tissue accumulated in model control group,while a significant decrease of perirenal and inguinal adipose tissue in ezetimibe group was observed accompanied by a reduction of histological steatosis.The liver MWR was（ 17. 64 ± 8. 97） in normal control group,（ 270. 28 ± 110. 44） in model control group and（ 57. 19 ±27.49） in ezetimibe group（ P〈0.01）.The PUI of the livers was（ 0.035±0.023） in normal control group,（ 0.007 2±0.005 3） in model control group and（ 0.024±0.019） in ezetimibe group（ P〈0.01）.Compared with normal control group,serum levels of TC,TG,FFA,LDL-C,ALT and AST in model control group increased significantly（ P〈0. 01）. However,ezetimibe significantly lowered the serum levels of TC,TG,FFA,LDL-C,ALT and AST（ P〈0.01） in hamsters fed with HFD. Conclusion -1H-MRS and MRI could be used to construct the evaluation system of nonalcoholic fatty liver disease in hamsters and ezetimibe can significantly improve nonalcoholic fatty liver disease in HFD-fed hamsters.