刺梨黄酮对高脂血症小鼠血脂的影响及其分子机制  

Effect of Rosa roxburghii flavonoids on blood lipid levels in hyperlipidemic mice and its molecular mechanism

作　　者：唐嘉琦 徐丽霞 张青 张紫麒 宋萍萍 付凌云[2,3] TANG Jiaqi;XU Lixia;ZHANG Qing;ZHANG Ziqi;SONG Pingping;FU Lingyun(School of Biology and Engineering,Guizhou Medical University,Guian New Area 561113,Guizhou,China;The State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guian New Area 561113,Guizhou,China;School of Pharmacy&Key Laboratory of Optimal Utilization of Natural Medicine Resources,Guizhou Medical University,Guian New Area 561113,Guizhou,China)

机构地区：[1]贵州医科大学生物与工程学院,贵州贵安新区561113 [2]贵州医科大学药用植物功能与应用国家重点实验室,贵州贵安新区561113 [3]贵州医科大学药学院&天然药物资源最佳利用重点实验室,贵州贵安新区561113

出　　处：《贵州医科大学学报》2025年第3期325-335,共11页Journal of Guizhou Medical University

基　　金：国家自然科学基金(U1812403-4-4);贵州省科技计划(黔科合中引地[2023]003);贵州省卫生健康委员会科学基金项目(gzwkj2021-530);贵州省中药管理局中医药、民族医药科学技术研究课题(QZYY-2022-035);贵州省大学生创新创业训练计划(S202110660075,S202210660059)。

摘　　要：目的通过建立高脂血症(hyperlipidemia,HLP)小鼠模型,利用转录组学探索刺梨黄酮对HLP小鼠血脂和肝功能的影响及其潜在分子机制。方法将96只6周龄C57BL/6J雄性小鼠随机均分为12组,包括对照组(C组)、HLP模型组(M组)、阳性药物组(PC组)和9组刺梨黄酮组[槲皮素(quercetin,QU)、杨梅素(myricetin,MY)和山奈素(kaempferol,KA)3种黄酮,各低、中、高3个浓度],分别进行相应的饮食和灌胃;6周后检测小鼠眼球血清中TG、TC、HDL、LDL、AST和ALT水平,确定各黄酮的相对最佳作用浓度;使用HE染色和油红O染色分析肝脏组织变化和肝细胞脂质积累程度;转录组分析刺梨黄酮作用下与脂质代谢相关的差异表达基因及其可能信号通路;RT-PCR和Western blot技术对关键基因和蛋白进行验证。结果血脂结果显示刺梨黄酮降血脂效果的最佳浓度,QU_(M)为200 mg/(kg·d)、MY_(M)为75 mg/(kg·d)和KA_(H)为100 mg/(kg·d);与C组相比,M组血清TG、TC、LDL和ALT水平显著上升且HDL显著降低(P<0.01),肝细胞中出现大量脂肪空泡并伴随着脂肪变性;相较于M组,QU_(M)组、MY_(M)组和KA_(H)组的TG、LDL及ALT水平降低(P<0.05),QU_(M)组的TC水平下降(P<0.05);血脂和肝功能结果显示,QU_(M)组效果优于MY_(M)组和KA_(H)组,且肝细胞内脂质沉积也得到明显改善;转录组分析揭示PPARα通路上的CYP4A14是3种刺梨黄酮共同影响的关键基因;RT-PCR和Western blot分析结果为3个黄酮组的CYP4A14表达均高于M组、且QU_(M)组>KA_(H)组>MY_(M)组(P<0.01)。结论刺梨3种黄酮成分均具有不同程度的降血脂作用,并能相应改善小鼠肝细胞脂质积累与脂肪变性,其共同机制可能与调节PPARα通路上关键基因CYP4A14的表达有关。Objective To establish a hyperlipidemia(HLP)mouse model and to explore the effects of Rosa roxburghii flavonoids on blood lipid levels and liver function in HLP mice,and the potential molecular mechanism by transcriptomic analysis.Methods Ninety-six 6-week-old male C57BL/6J mice were randomly divided into 12 groups:the control group(C),a hyperlipidemia model group(M),a positive control group(PC),and nine groups treated with Rosa roxburghii flavonoids,including quercetin(QU),myricetin(MY),and kaempferol(KA)at low,medium,and high concentrations,separately.Six weeks after treatment,the levels of TG,TC,HDL,LDL,AST,and ALT in mice eye serum were measured to determine the relative optimal concentrations of each flavonoid.Liver tissue changes and the degree of hepatic lipid accumulation were analyzed using HE staining and oil red O staining.Transcriptome analysis was conducted to identify differentially expressed genes related to lipid metabolism under the action of Rosa roxburghii flavonoids and their potential signaling pathways.RT-PCR and Western blot techniques were employed for the validation of key genes and proteins.Results The blood lipid results showed that the optimal reducing-blood-fat concentrations of Rosa roxburghii flavonoids were QU_(M)[200 mg/(kg·d)],MY_(M)[75 mg/(kg·d)],and KA_(H)[100 mg/(kg·d)].Compared with group C,significant increases in serum TG,TC,LDL,and ALT levels were observed in group M,with significant decrease in HDL(P<0.01),accompanied by extensive vacuolation and lipid degeneration in hepatocytes.Compared with group M,TG,LDL,and ALT levels(P<0.05)were reduced in QU_(M),MY_(M),and KA_(H) groups.Additionally,TC levels decreased in QU_(M) group(P<0.05).The blood lipid and liver function results showed that QU_(M) group exhibited superior effects compared with MY_(M) and KA_(H) groups,with a significant improvement in intrahepatic lipid deposition.Transcriptome analysis revealed that CYP4A14 on the PPARαpathway was the core gene jointly affected by the three Rosa roxburghii flavonoids.RT-

关 键 词：高脂血症 刺梨黄酮 转录组分析 槲皮素 杨梅素 山奈素 

分 类 号：R589.2[医药卫生—内分泌]