莪术愈创木烷型倍半萜化合物改善高脂饲料ApoE-/-小鼠脂质代谢和肝脏脂肪变性的机制研究

The study of Zedoary guaiacol sesquiterpene compound improve lipid metabolism and liver steatosis in ApoE-/-mice fed with high-fat diet

目的观察莪术愈创木烷型倍半萜化合物改善高脂饲料ApoE-/-小鼠脂质代谢和肝脏细胞脂肪变性的作用。方法8周龄SPF级雄性ApoE-/-小鼠30只,随机分为模型组、倍半萜治疗组(10 mg/kg)和阿托伐他汀治疗组(10 mg/kg);同源C57/BL6小鼠10只,作为正常对照组。模型组和正常对照组给予等体积生理盐水灌胃。各组小鼠干预12周,称重,麻醉取血,处死动物,检测血脂水平和肝功能等;肝脏切片油红O染色,观察肝脏脂肪滴含量;HE染色观察肝细胞损伤的程度;免疫组化检测肝脂酶(hepatic lipase,LIPC)蛋白表达的水平。结果实验12周时,和正常对照组相比,模型和各给药组小鼠体质量变化无统计学差异。与正常对照组小鼠相比,模型组小鼠总胆固醇(total cholesterol,TC)、甘油三酯(triacylglycerol,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-c)明显升高(P<0.01);与模型组相比,倍半萜组和阿托伐他汀组小鼠TC和LDL-c明显下降(P<0.01)。与正常对照组相比,模型组小鼠肝脏细胞大量脂滴形成、排列紊乱;倍半萜和阿托伐他汀组肝细胞脂滴减少,排列整齐。与正常对照组相比,模型组小鼠谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)和碱性磷酸酶(alkaline phosphatase,AKP)水平明显升高(P<0.05);与模型组相比,倍半萜组ALT、AST明显下降(P<0.01),阿托伐他汀治疗组降低不明显(P>0.05)。和模型组相比,倍半萜组小鼠肝脏LIPC蛋白表达明显升高(P<0.05)。结论倍半萜可改善高脂饮食ApoE-/-小鼠脂质代谢紊乱,抑制肝脏细胞脂肪变性,减轻肝细胞损伤,其机理可能与升高LIPC蛋白表达有关。

Objective To observe the effects of Guaiacane type sesquiterpene compound from Zedoary turmeric on lipid and liver cell steatosis in ApoE-/-mice fed with high fat diet.Methods Thirty SPF male ApoE-/-mice aged 8 weeks were randomly divided into the model group,the sesquiterpene treatment group(10 mg/kg/d)and the atorvastatin treatment group(10 mg/kg).Ten mice from homologous C57/BL6 were used as the normal control group.The model group and the normal control group were given equal volume of normal saline intragastric administration.After 12 weeks of intervention,the mice in each group were weighed and anesthetized for blood sampling.All the mice were sacrificed for blood lipid level and liver function.The content of fat droplets in liver slices were observed by oil-red O staining,the degree of liver cell injury was observed by HE staining,and the expression level of liver lipase(LIPC)was detected by immune histochemistry.Results At 12 weeks of the experiment,compared with the normal control group,there was no statistically significant difference in the body weight of mice in the model group and each administration groups.Compared with the normal control group,total cholesterol(TC),triglyceride(TG)and low density lipoprotein(LDL-c)in the model group were significantly increased(P<0.01);compared with the model group,the levels of TC and LDL-c in sesquiterpene group and atorvastatin group were significantly decreased(P<0.01).Compared with the normal control group,liver cells in the model group formed a large number of lipid droplets,and liver cells were disordered;sesquiterpene and atorvastatin improved significantly after treatment.Compared with the normal control group,the levels of ALT,AST and ALP in the model group were significantly increased(P<0.05);compared with the model group,ALT and AST were significantly decreased in the sesquiterpene group(P<0.01),but not in the atorvastatin group(P>0.05);compared with the model group,the LIPC expression in tissues of liver in the sesquiterpene group was significantly increased(P<0.05).Conclusion Sesquiterpene can improve the expression of LIPC,improve lipid metabolism disorder,inhibit liver cell steatosis and reduce liver cell injury in ApoE-/-mice fed with high fat diet.