GO-CoA-Tat改善脂肪肝小鼠脂质代谢和氧化应激

GO-CoA-Tat improves lipid metabolism and oxidative stress in mice with fatty liver disease

目的探讨饥饿素O-酰基转移酶(ghrelin O-acyltransferase,GOAT)抑制剂GO-CoA-Tat对高脂饮食(high-fat diet,HFD)诱导的非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)小鼠脂质代谢和氧化应激的影响。方法选择C57BL/6雄性小鼠24只,分为对照组、HFD组和GO-CoA-Tat组,每组8只。对照组给予标准饮食,HFD组和GO-CoA-Tat组均给予HFD,GO-CoA-Tat组喂养第3周起每天腹腔注射GO-CoA-Tat。每周测量小鼠食物摄入量和小鼠体质量。喂养8周后采集血清及肝脏样本,测量肝脏质量,并采用油红O染色检测肝脏脂滴形成情况;检测并比较3组小鼠血清三酰甘油(triglyceride,TG)、总胆固醇(total cholesterol,TC)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)和肝脏谷胱甘肽(glutathione,GSH)、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)。结果HFD组小鼠喂养8周后出现明显的肝脏脂肪变性;与HFD组相比,GO-CoA-Tat组脂肪变性明显缓解。与HFD组相比,GO-CoA-Tat组小鼠食物摄入量减少、体质量减小、肝脏质量减小(P<0.05)。与HFD组相比,GO-CoA-Tat组小鼠肝脏TG含量降低,血清TG和TC降低(P<0.05);肝脏GSH、SOD浓度升高(P<0.01),MDA浓度下降(P=0.005);血清ALT和AST降低(P<0.05)。结论GO-CoA-Tat可改善NAFLD小鼠肝脏的脂质代谢和氧化应激,从而发挥肝脏保护作用。

Objective To investigate the effects of GO-CoA-Tat,an inhibitor of ghrelin O-acyltransferase(GOAT),on lipid metabolism and oxidative stress in mice with non-alcoholic fatty liver disease(NAFLD)induced by high-fat diet(HFD).Methods Twenty-four C57BL/6 male mice were selected and divided into control group,HFD group and GO-CoA-Tat group,with 8 mice in each group.The mice in control group was given standard diet,the mice in HFD group and GO-CoA-Tat group were rd given HFD,and the mice in GO-CoA-Tat group was given daily intraperitoneal injection of GO-CoA-Tat from 3 week of feeding.Food intake and body mass of mice were measured weekly.After 8 weeks,serum and liver samples were collected,liver weight was measured,and fat droplets were detected by hepatocyte oil red O staining;biochemical indexes such as serum triglyceride(TG),total cholesterol(TC),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and oxidative stress indexes of liver such as glutathione(GSH),superoxide dismutase(SOD)and malondialdehyde(MDA)were measured.Results Hepatic steatosis was observed after feeding with HFD for 8 weeks,which was significantly relieved in GO-CoA-Tat group compared with HFD group.Compared with HFD group,the food intake,body weight and liver weight of mice in GO-CoA-Tat group decreased(P<0.05).Compared with HFD group,the content of TG in liver of mice in GO-CoA-Tat group decreased,the concentrations of serum TG and TC decreased(P<0.05),and the concentrations of liver GSH and SOD increased(P<0.01),liver MDA decreased(P=0.005),and the serum ALT and AST decreased(P<0.05).Conclusion GO-CoA-Tat can improve lipid metabolism and oxidative stress in the liver of NAFLD mice,thus play a protective role in the liver.