大叶茜草素对高脂诱导小鼠非酒精性脂肪肝的影响

目的探讨大叶茜草素(SW)对高脂饲料诱导的小鼠非酒精性脂肪肝(Nonalcoholic fatty liver disease,NAFLD)的作用机制。方法将120只雄性C57小鼠随机分为正常组,模型组,阿托伐他汀组,SW低、中、高剂量组。正常组小鼠食用标准饮食,其他各组小鼠均采用高脂(含有59.3%脂肪)饲料喂养6周建立NAFLD模型。从第5周开始,阿托伐他汀组给予阿托伐他汀20 mg/kg灌胃治疗,SW低、中、高剂量组分别给予SW 20 mg/kg、40 mg/kg、80 mg/kg灌胃,正常组和模型组灌胃等体积生理盐水。检测小鼠血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)。采用苏木素-伊红(HE)染色检测小鼠肝脏病理学改变。检测小鼠血清细胞因子(IL-1β、IL-6、TNF-α)水平;采用蛋白印迹法检测小鼠肝脏乙酰辅酶A羧化酶-1(ACC1)、脂肪酸合成酶(FAS)、固醇调节元件结合蛋白-1C(SREBP-1c)、肝X受体(LXRs)、腺苷酸激活蛋白激酶(AMPK)、过氧化物酶体增殖物激活受体γ(PPAR-γ)、PPAR辅激活因子1α(PGC-1α)和NF-κB蛋白表达。结果SW可显著降低小鼠血清ALT、AST、TG、TC、LDL-C水平及细胞因子(IL-1β,IL-6,TNF-α)水平;明显升高血清HDL-C水平;HE染色显示,SW能够明显改善模型组小鼠肝脏组织胞质内脂滴积聚和炎性细胞浸润的病理学改变。同时,蛋白印迹结果显示,SW明显降低LXRs、ACC1和FAS水平,升高SREBP-1c、PPAR-γ水平蛋白水平;还可明显升高AMPK、PPAR-γ、PGC-1α水平,降低p-NF-κB水平。结论SW能明显改善高脂诱导小鼠NAFLD的病理状态,其机制可能与调控肝脏脂肪合成与肝脏炎症反应有关。

Effect of Swertiamarin on High-Fat-Induced Nonalcoholic Fatty Liver in Mice

Objective To explore the mechanism of swertiamarin(SW)on high-fat diet-induced nonalcoholic fatty liver disease(NAFLD)in mice.Methods 120 male C57 mice were randomly divided into normal group,model group,atorvastatin group,SW low,medium and high dose groups.Mice in the normal group were fed a standard diet,and mice in other groups were fed with high-fat(containing 59.3%fat)diet for 6 weeks to establish the NAFLD model.From the 5;week,the atorvastatin group was given atorvastatin 20 mg/kg by gavage,and the SW low,middle and high dose groups were given SW 20 mg/kg,40 mg/kg,and 80 mg/kg by gavage,respectively.Stomach,normal group and model group were gavaged with equal volume of normal saline Commercial kits were used to detect serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TC),total cholesterol(TG),low density lipoprotein(LDL-C)and high density lipoprotein(HDL-C)in mice.Hematoxylin-eosin(HE)staining was used to detect the pathological changes of mouse liver.The levels of cytokines(IL-1β,IL-6,TNF-α)in mouse serum were detected by commercial kit.Acetyl coenzyme a carboxylase(ACC1),fatty acid synthase(FAS),sterol regulatory element binding protein(SREBP-1 c),liverx receptor(LXRs),adenylate activated protein kinase(AMPK),peroxisome proliferator activated receptorα(PPAR-γ).Result SW could significantly reduce serum ALT,AST,TG,TC,LDL-C levels and cytokines(IL-1β,IL-6,TNF-α)levels in mice;significantly increase serum HDL-C levels;HE staining It was shown that SW could significantly improve the pathological changes of lipid droplet accumulation and inflammatory cell infiltration in the liver tissue of mice in the model group.At the same time,Western blot results showed that SW significantly decreased the levels of LXRs,ACC1 and FAS,and increased the levels of SREBP-1 c and PPAR-γ;it also significantly increased the levels of AMPK,PPAR-γ,PGC-1α,and decreased p-NF-κB levels.Conclusion These results indicate that SW can significantly improve NAFLD induced by high fat in mice,and its mechanism is related to the regulation of liver fat synthesis and liver inflammation.