摘要
目的:通过研究荷叶碱对小鼠动脉粥样硬化(AS)血管炎症及基质金属蛋白酶(MMPs)的影响来阐明其抗AS机制。方法:实验采用高脂饮食诱导构建AS小鼠模型,根据不同饮食分为对照组、AS组、低剂量荷叶碱组和高剂量荷叶碱组。12周后分析荷叶碱对血脂、血清炎性因子(TNF-α、MCP-1)、血管壁炎性因子(IL-1β、TNF-α、MCP-1、NF-κB)的影响,并检测血管壁中MMP-2、9及其抑制物(TIMP-2)的基因表达。结果:荷叶碱有效降低了体重、总胆固醇(TC)、高/低密度脂蛋白胆固醇(HDL-C、LDL-C)及血清炎症(P<0.05),且高剂量组尤为明显(P<0.05),但对高TG血症改善不大(P>0.05)。Real-Time PCR结果显示,AS组小鼠主动脉壁硬化段组织的炎性因子(IL-1β、TNF-α、MCP-1、NF-κB)表达均显著上调(P<0.05),荷叶碱干预后明显回落(P<0.05),且与剂量相关,但MCP-1mRNA除外(P>0.05)。MMP-2,9mRNA亦呈相同变化趋势,而TIMP-2在荷叶碱干预后显著上调(P<0.05),且在大剂量组表达尤为明显(P<0.05)。结论:荷叶碱能够降低血脂异常及血清炎症,并减少血管壁炎症,这一作用可能与调控NF-κB有关;同时荷叶碱可能通过调控MMP-2、9及TIMP-2进一步影响动脉粥样硬化的发生发展。
Objective：In this study,the effects of nuciferine on vascular inflammation and matrix metalloproteinases in mouse with atherosclerosis were investigated and the molecular mechanism was clarified.Method：The model was induced by high-fat diet and treated by nuciferine.The mice were divided into four groups according to the different diet：control group,AS group,low dose group,high dose group.Several indics were analyzed,including serum lipid,serum inflammatory cytokines（TNF- α,MCP-1）,inflammation gene in vascular wall（IL-1β,TNF-α,MCP-1,NF-κB）and matrix metalloproteinases（MMP-2,9and TIMP-2）.Result：Nuciferine effectively reduced the body weight,total cholesterol（TC）,high/low density lipoprotein cholesterol（HDL-C,LDLC）and serum inflammation（P〈0.05）,especially in the high dose group（P〈0.05）,but showed little improvement on hypertriglyceridemia（P〉0.05）.In addition,Real-Time PCR suggested that the expressions of inflammatory gene in aortic wall tissue of AS mice（IL-1β,TNF-α,MCP-1,NF-κB）were significantly increased（P〈0.05）,but attenuated after nuciferine treatment showing a dose related（P〈0.05）,except MCP-1 mRNA（P〉0.05）.The levels of MMP-2,9mRNA also showed the same change and the expressions of TIMP-2mRNA were significantly up-regulated after nuciferine treatment（P〈0.05）,especially in the high dose group（P〈0.05）.Conclusion：Nuciferine could attenuate the hyperlipidemia and serum inflammatory factors,and lower the inflammation in the vessel wall,which may be related to the regulation of NF-κB.And it might inhibit the development of atherosclerosis by regulating MMP-2,9and TIMP-2.
出处
《临床心血管病杂志》
CAS
CSCD
北大核心
2015年第1期97-100,共4页
Journal of Clinical Cardiology
关键词
荷叶碱
动脉粥样硬化
炎症
基质金属蛋白酶
nuciferine
atherosclerosis
inflammation
matrix metalloproteinase
