富含蒙花苷的野菊花提取物调节脂质组成及胆固醇代谢改善肝损伤的机制研究  

Mechanism Study of Linarin Enriched Extract from Flos chrysanthemi Indici on Improving Liver Injury by Regulating Lipid Profiles and Cholesterol Metabolism

作　　者：庄振杰[1] 罗燕[1] 苏洁[2] 柳银兰[1] 吕圭源[2] Zhuang Zhenjie;Luo Yan;Su Jie;Liu Yinlan;Lv Guiyuan(the Affiliated Hospital of Hangzhou Normal University,Hangzhou 310015;Chinese Medical University,Hangzhou 311402)

机构地区：[1]杭州师范大学附属医院,杭州310015 [2]浙江中医药大学,杭州311402

出　　处：《中药药理与临床》2020年第4期108-114,共7页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金(编号:81274123);浙江省自然科学基金(编号:LQ18H28003);杭州市科技局基金(编号:20170533B42)。

摘　　要：目的:前期发现富含蒙花苷的野菊花提取物能改善高脂高胆固醇饮食造成的肝损伤,本文从脂质角度对其机制进行进一步探讨。方法:通过高脂高胆固醇饮食诱导大鼠非酒精性脂肪性肝病模型,予以不同剂量蒙花苷提取物(15、30、60 mg/kg)干预,采用超高效液相色谱-飞行时间质谱仪检测肝脏脂质谱,荧光定量PCR法检测胆固醇代谢相关基因。结果:与正常对照组相比,模型对照组肝脏脂质谱改变,蒙花苷提取物60 mg/kg干预使肝脏脂质谱趋向于正常对照组。其中,与模型对照组比较,蒙花苷提取物60 mg/kg组肝脏n-3二十碳四烯酸类、12-羟-9-十八碳炔酸含量显著升高(P<0.01,P<0.05);两种尚不能确定亚类的磷脂类分子在模型对照组中的含量与正常对照组相比显著下调(P<0.05,P<0.01),在蒙花苷提取物60 mg/kg组含量与模型对照组相比显著升高(P<0.01)。荧光定量PCR结果显示,与正常对照组相比,促胆固醇排泄和抑制吸收相关基因ATP结合盒基因8(ABCG8)在模型对照组肝脏中显著下调(P<0.01)。蒙花苷提取物60 mg/kg组与模型对照组比较,ABCG8基因在肝脏和肠道表达均显著增加(P<0.05),ATP结合盒基因5(ABCG5)仅在肝脏显著增加(P<0.01)。结论:蒙花苷提取物通过促进胆固醇排泄,抑制胆固醇吸收降低肝脏胆固醇含量;通过改变肝脏脂质组成改善高脂高胆固醇饮食造成的肝损伤。Objective:Previous study showed that linarin enriched extract(Lin-extract) from flos Chrysanthemum indicum could ameliorate liver injury caused by high-fat and high-cholesterol diet(HFHC). In this study, potential mechanisms related to lipid metabolism is explored. Methods: Rat non-alcoholic fatty liver model was induced by high-fat and high-cholesterol diet, then different doses of Lin-extract(15, 30, and 60 mg/kg/d) were simultaneously administered. Ultra-performance liquid chromatography-time-of-flight mass spectrometer was employed to examine the lipid profiles of liver. Realtime PCR was performed to quantify the expression levels of cholesterol metabolism-related genes. Results: Compared with the normal diet, the HFHC diet significantly altered the liver lipid profiles, 60 mg/kg Lin-extract changed the pattern of lipid profile towards to that in the normal diet group, the contents of two undefined lipid molecules were significantly down regulated in the model group(P<0.01,P<0.05), the RT PCR result showed that the liver levels of ABCG8, a gene promoting cholesterol excretion and inhibiting its absorption were significantly down regulated(P<0.01). Compared with the model group, the liver levels of n-3 C20:4 n-3,6,9,15, 12-hydroxy-9-octadecynoic acid were significantly increased in 60 mg/kg Lin-extract group(P<0.01,P<0.05).The contents of two undefined lipid molecules were elevated in 60 mg/kg Lin-extract group(P<0.01), RT PCR results showed that the levels of ABCG8 mRNA in both the gut and the liver were increased in 60 mg/kg Lin-extract group(P<0.05), while ABCG5 mRNA level was only elevated in the liver by 60 mg/kg Lin-extract(P<0.01).Conclusion: Lin-extract might promote the cholesterol excretion, inhibit cholesterol absorption, decrease hepatic cholesterol accumulation, and then modify hepatic lipid profile,in order to improve the liver injury induced by HFHC-damage.

关 键 词：蒙花苷提取物 肝损伤 脂质谱 胆固醇代谢 

分 类 号：R285.5[医药卫生—中药学]