橙皮素对高脂血症仓鼠的降脂作用和肝脂肪变性的影响

Hypolipidemic Effect of Hesperetin on Hyperlipidemic Hamsters and its Effect on Hepatic Steatosis

目的:探讨橙皮素(HES)对高脂血症仓鼠的降脂作用、肝脂肪变性的影响及机制。方法:将18只雄性仓鼠均分为正常对照组(NC组)、高脂血症模型组(Model组)及HES干预组(HES组),NC组喂饲基础饲料、另2组喂饲高脂饲料,HES组仓鼠每日按照100 mg/kg剂量给予HES灌胃,其余2组仓鼠给予0.5%羧甲基纤维素钠灌胃处理,连续6周;于实验开始、实验第3周及第6周取血,测定3组仓鼠血清血脂四项[总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)]水平;于实验第6周检测3组仓鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)活性,检测仓鼠肝脏组织中TC、TG、总抗氧化能力(TAC)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平及胆固醇调节元件结合蛋白2(Srebp 2)、3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)mRNA表达水平,采用HE染色观察各组仓鼠肝脂肪变性程度。结果:与NC组比较,Model组仓鼠第3周及第6周末血清中TC、TG、LDL-C水平明显升高(P<0.05);实验第6周末,Model组血清中ALT、AST活性升高,肝脏中TC、TG、MDA含量及Srebp2、HMGCR的mRNA表达水平升高,TAC、SOD水平下降,差异有统计学意义(P<0.05);与Model组比较,HES组第3周和第6周血清中TC、TG、LDL-C水平下降(P<0.05),实验第6周,HES组血清中ALT、AST活性下降,肝脏中TC、TG、MDA含量及Srebp2、HMGCR的mRNA表达水平下降,TAC、SOD水平升高,差异有统计学意义(P<0.05);实验第6周,HE染色显示,Model组仓鼠肝细胞体积明显增大且大小不一,可见大小不等的圆形空泡,肝小叶结构模糊不清,HES组仓鼠肝细胞圆形空泡数量及面积明显减少,可见较为清晰的肝小叶结构。结论:HES能有降低血脂水平,减轻高脂血症仓鼠肝脂肪变性,其护肝机制可能与其降脂和抗氧化活性有关。

Objective:To investigate the effect and mechanism of hesperetin(HES)on lipid-lowering and hepatic steatosis in hyperlipidemic hamsters.Methods:18 male hamsters were randomly divided with equal number into normal control group(NC group),hyperlipidemia model group(Model group)and hesperetin intervention group(HES group).The NC group was fed with standard diet,and the other groups were fed with high-fat containing diet.Hamsters in the HES group were administered intragastrically hesperetin(100 mg/kg),while other groups were administered intragastrically 0.5%sodium carboxymethyl cellulose for 6 weeks.The level of serum lipids were measured in the beginning of test,3 weeks and 6 weeks after test:total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C).Following indicators of all groups were tested 6 weeks after test:activity of serum alanine transaminase(ALT)and aspartate transaminase(AST),TC,TG,total antioxidant capacity(TAC),superoxide dismutase(SOD),malondialdehyde(MDA),level of MDA,expression level of sterol regulatory element binding genes(Srebp 2)and 3-hydroxyl-3-methyl-HMGCR-A-reducase(HMGCR);hepatic steatosis degree in hamsters were observed with HE staining.Results:The levels of serum TC,TG and low density lipoprotein cholesterol(LDL-C)in Model group in 3 rd week and 6 th week were effectively increased(P<0.05);by the end of 6 th week,activity of ALT and AST of Model group increased,hepatic content of TC,TG,MDA as well as mRNA expression level of Srebp2 and HMGCR increased,while level of TAC and SOD obviously decreased,differences were statistically significant(P<0.05).Compared with Model group,HES group showed lowered level of TC,TG and LDL-C in serum in 3 rd and 6 th week(P<0.05).In 6 th week,activity of ALT and AST in serum of HES group was lowered,hepatic TC,TG and MDA content as well as mRNA expression level of Srebp2 and HMGCR were lowered,levels of TAC and SOD were increased,differences were statistically significant(P<0.05).In 6 th week,HE staining showed that hepatocyte size of Model group was obviously enlarged in different sizes;round vacuole in various sizes were observed,hepatic lobule showed blurry structure;in HES group,round vacuole count and size were obviously reduced,relatively clear hepatic lobule could be observed.Conclusions:Hesperetin have hypolipidemic effect and can attenuate hepatic steatosis in hyperlipidemic hamsters.Its liver protection mechanism may be related to hypolipidemic efficacy and antioxidant activity.