普洱茶素Ⅱ改善高脂血症ApoE-/-小鼠动脉粥样硬化作用机制研究  

Mechanism of puerin Ⅱ on improving atherosclerosis in ApoE-/- mice with hyperlipidemia

作　　者：王鑫玉 赵一慕 高云 阴紫钰 王凌潇 马家乐 赵云芳[1] 郑姣[1] 李军[1,2] WANG Xin-yu;ZHAO Yi-mu;GAO Yun;YIN Zi-yu;WANG Ling-xiao;MA Jia-le;ZHAO Yun-fang;ZHENG Jiao;LI Jun(Beijing Research Institute of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102488,China;School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]北京中医药大学中医药研究院中药现代研究中心,北京102488 [2]北京中医药大学中药学院,北京102488

出　　处：《中草药》2023年第4期1157-1163,共7页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(82074050);国家重点研发计划(2018YFC1706400)。

摘　　要：目的 研究普洱茶素Ⅱ对高脂血症诱发动脉硬化ApoE基因敲除小鼠(ApoE-/-)的治疗效果及作用机制。方法ApoE-/-小鼠通过喂养高脂饲料建立动脉粥样硬化动物模型,造模成功后将小鼠随机分为对照组、模型组、阿托伐他汀(30mg/kg)组和普洱茶素Ⅱ低、高剂量(50、100 mg/kg)组,给药6周后检测小鼠血浆总胆固醇(total cholesterol,TC)、三酰甘油(triglycerides,TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)和非高密度脂蛋白胆固醇(nonhigh density lipoprotein cholesterol,non-HDL-C)水平,以及主动脉流出道斑块面积等指标的差异。体外培养人脐静脉内皮细胞HUVEC和人外周血单核细胞THP-1,检测普洱茶素Ⅱ对氧化低密度脂蛋白(oxidized low density protein,ox-LDL)诱发单核与内皮细胞黏附的影响,利用Western blotting对蛋白激酶B(protein kinase B,Akt)/核因子-κB(nuclear factor-κB,NF-κB)/血管细胞黏附因子(vascular cell adhesion molecule-1,VCAM-1)通路相关蛋白表达进行检测。结果 普洱茶素Ⅱ显著抑制了高脂饮食诱导ApoE-/-小鼠的体质量、肝脏质量、肝脏指数、附睾脂肪质量和附睾脂肪指数(P<0.05、0.01),降低血浆TC、TG、non-HDL-C水平(P<0.05、0.01),升高HDL-C水平(P<0.05),减少主动脉流出道脂质沉积。体外实验证实,普洱茶素Ⅱ显著抑制HUVEC与THP-1细胞间的黏附(P<0.05),抑制ox-LDL诱导的HUVEC细胞中VCAM-1、单核细胞趋化蛋白-1(monocyte chemotactic protein-1,MCP-1)和Akt/NF-κB通路相关蛋白表达(P<0.05、0.01)。结论 普洱茶素Ⅱ能够显著改善ApoE-/-小鼠的肥胖、脂代谢紊乱、主动脉斑块沉积,通过调控Akt/NF-κB/VCAM-1通路抑制内皮细胞与单核细胞的黏附,进而抑制动脉粥样硬化的发生与发展。Objective To study the therapeutic effect and mechanism of puerin Ⅱ on ApoE-/-mice with hyperlipidemia induced atherosclerosis. Methods ApoE-/-mice were fed high-fat diet to establish atherosclerotic animal models. After successful modeling,mice were randomly divided into control group, model group, atorvastatin(30 mg/kg) group and puerin Ⅱ low-and high dose(50, 100mg/kg) groups. After 6 weeks of administration, the difference of total cholesterol(TC), triglycerides(TG), high density lipoprotein cholesterol(HDL-C) and non-high density lipoprotein cholesterol(non-HDL-C) levels, as well as plaque area of aortic sinus were detected. Human umbilical vein endothelial cells(HUVEC) and human peripheral blood mononuclear cells(THP-1) were cultured in vitro. The effects of puerin Ⅱ on adhesion of monocytes to endothelial cells induced by oxidized low density lipoprotein(ox-LDL)were detected. Western blotting was used to detect protein kinase B(Akt)/nuclear factor-κB(NF-κB)/vascular cell adhesion molecule-1(VCAM-1) pathway related protein expressions was detected. Results Puerin Ⅱ significantly inhibited the body weight, liver weight, liver index, epididymal fat weight, and epididymal fat index(P < 0.05, 0.01), decreased TC, TG, and non-HDLc levels in plasma(P < 0.05, 0.01), increased HDL-C level(P < 0.05), reduced lipid deposition in aortic sinus. In vitro experiments confirmed that puerin Ⅱ significantly inhibited the adhesion between HUVEC and THP-1 cells(P < 0.05), inhibited VCAM-1, monocyte chemoattractant protein-1(MCP-1), and Akt/NF-κB pathway related protein expressions in HUVEC cells induced by ox-LDL(P <0.05, 0.01). Conclusion Puerin Ⅱ can significantly improve the obesity, lipid metabolism disorder, and aortic plaque deposition of ApoE-/-mice by regulating Akt/NF-κB/VCAM-1 pathway, inhibit the adhesion of endothelial cells and monocytes, thereby inhibiting the occurrence and development of atherosclerosis.

关 键 词：普洱茶素Ⅱ 高脂血症 ApoE-/- 脂代谢异常 动脉粥样硬化 蛋白激酶B/核因子-κB通路 

分 类 号：R285.5[医药卫生—中药学]