摘要
目的:探讨氯化腺苷对腹主动脉缩窄(AAC)致大鼠心肌肥厚时TLR4及其介导的信号通路的作用。方法:大鼠采用结扎腹主动脉的方法制备AAC模型,1周后给予大鼠2-氯化腺苷0.3、0.6、1.2 mg/kg,每天一次,共12周;计算心脏质量指数(HMI)和左心室质量指数(LVMI);测定左心室收缩压(LVSP)、左心室舒张末压(LVEDP)和左心室内压最大升降速率(±dp/dtmax);采用逆转录-聚合酶链反应(RT-PCR)测定心肌心钠素mRNA(ANP mRNA)表达;ELISA法检测心肌组织TNF-α、IL-1β的含量;Western blot法检测心肌组织IκBα、TLR4的蛋白含量。结果:与假手术组相比,AAC模型组的大鼠,IκBα蛋白量明显降低,其他指标均显著增高;同模型组相比,2-氯化腺苷1.2 mg/kg组的HMI,LVMI,LVSP,LVEDP和±dp/dtmax均显著降低;2-氯化腺苷0.6、1.2mg/kg组的ANP mRNA表达和TLR4蛋白量明显下降,IκBα蛋白量明显升高;2-氯化腺苷0.3、0.6、1.2 mg/kg组心肌组织TNF-α、IL-1β的含量均显著减少。结论:氯化腺苷可以有效抑制AAC大鼠心肌肥厚,抑制炎症因子含量的增加,其作用机制可能同TLR4及其介导的NF-κB通路有关。
Objective：To explore the effect of adenosine on TLR4 and mediated signal path induced by abdominal aorta constriction in rats.Methods： Myocardial hypertrophy model in SD rats was established by adopting abdominal aorta constriction（AAC）.2-CADO0.3,0.6,1.2 mg/kg were given to the rats for 11 weeks;Heart mass index（HMI） and left ventricular mass index（LVMI） were detected;Left ventricular systolic pressure（LVSP）;left ventricular end-diastolic pressure（LVEDP）,and maximum rate of rise/decrease of LVSP（± dp/dtmax） were detected;mRNA expression of heart atrial natriuretic peptide（ANP） was observed by RT-RCR;the expression of TNF-α,IL-1β was determined by ELISA;the expression of IκBα and TLR4 were measured by Western.Results： Compared with sham group,IκBα significantly decreased and other indicators significantly elevated in all index in AAC group;Compared with AAC group,2-CADO 1.2 mg/kg decreased HMI,LVMI,LVSP,LVEDP and ± dp/dtmax.;2-CADO 0.6,1.2 mg/kg could also remarkably down-regualte the overexpressions of ANP mRNA and TLR4 induced by AAC and significantly improved IκBα level;TNF-α and IL-1β contents effectively decreased by 2-CADO 0.3,0.6,1.2 mg/kg.Conclusion： ADO can inhibit the increased content of inflammation factor in AAC rats and has a protective effect on protects the hypertrophic myocardium,which is partially via attenuating the expression of TLR4/NF-κB.
出处
《中药药理与临床》
CAS
CSCD
北大核心
2013年第3期57-60,共4页
Pharmacology and Clinics of Chinese Materia Medica
基金
辽宁省科技计划项目(2009225010-40)
辽宁省教育厅创新团队项目(2009T064)
关键词
腺苷
心肌肥厚
腹主动脉缩窄
心钠素
炎症因子
adenosine（腺苷） myocardial hypertrophy abdominal aorta construction atrial natriuretic peptide inflammation factor
