阿托伐他汀改善急性心肌梗死小鼠炎症诱导性脂肪因子代谢紊乱

发布时间：2018-05-09 07:52

本文选题：急性心肌梗死 + 动脉粥样硬化　；参考：《中南大学学报(医学版)》2017年07期

【摘要】：目的:明确急性心肌梗死(acute myocardial infarction,AMI)期间炎症激活与脂肪因子代谢紊乱的关系,探讨阿托伐他汀的潜在治疗作用及其机制。方法:32只C57BL/6小鼠随机分为4组:假手术组、AMI组、小剂量阿托伐他汀组[2 mg/(kg.d)]和大剂量阿托伐他汀组[20 mg/(kg.d)]。干预3周后,后3组采用冠状动脉结扎术构建AMI模型,测定小鼠血浆高敏C反应蛋白(high sensitive C reaction protein,hs-CRP)浓度,以及血浆和组织中脂联素和抵抗素的表达。体外诱导小鼠3T3L1前脂肪细胞分化成熟后,观察氧化低密度脂蛋白(oxidized low density lipoprotein,ox-LDL)对细胞脂联素和抵抗素表达的影响,并研究不同剂量阿托伐他汀干预对ox-LDL所致脂肪因子代谢紊乱的作用。结果:动物实验显示AMI小鼠血浆hs-CRP和抵抗素浓度均明显升高,而脂联素明显降低。阿托伐他汀预处理呈剂量依赖性抑制AMI小鼠血浆上述因子浓度变化。hs-CRP和抵抗素在小鼠脂肪组织中表达也观察到类似的结果。相关性分析显示血浆hsCRP浓度与抵抗素呈正相关,而与脂联素呈负相关。体外试验显示ox-LDL刺激可上调脂肪细胞抵抗素表达,同时降低脂联素表达,而阿托伐他汀呈剂量依赖性逆转上述ox-LDL效应。结论:AMI小鼠体内炎症激活导致脂肪因子代谢紊乱,而阿托伐他汀通过抗炎作用可改善此类脂肪因子代谢紊乱。
[Abstract]:Objective: to investigate the relationship between inflammatory activation and metabolic disorder of fat factors during acute myocardial infarction (AMI), and to explore the potential therapeutic effect of Atto vastatin and its mechanism. Methods Thirty-two C57BL/6 mice were randomly divided into four groups: sham operation group, low dose Atto vastatin group [2 mg / kg 路d] and high dose Atto vastatin group [20 mg / kg 路d]. After 3 weeks of intervention, the AMI model was established by coronary artery ligation in the last three groups. The plasma Gao Min C-reactive protein high sensitive C reaction protein hs-CRP was measured, and the expression of adiponectin and resistin in plasma and tissue were measured. The effects of oxidized low density lipoprotein (ox-LDL) on the expression of adiponectin and resistin were observed after inducing the differentiation and maturation of mouse 3T3L1 preadipocytes in vitro. The effects of different doses of Atto vastatin on the metabolic disorder of fat factors induced by ox-LDL were studied. Results: the plasma levels of hs-CRP and resistin in AMI mice were significantly increased, but adiponectin was significantly decreased. In a dose-dependent manner, Atto vastatin inhibited the expression of hs-CRP and resistin in plasma of AMI mice in a dose-dependent manner. Similar results were observed in adipose tissue of mice. Correlation analysis showed that plasma hsCRP concentration was positively correlated with resistin and negatively correlated with adiponectin. In vitro experiments showed that ox-LDL stimulation could up-regulate the expression of resistin in adipocytes and decrease adiponectin expression, while Atto vastatin reversed the above effects of ox-LDL in a dose-dependent manner. Conclusion Activation of inflammation in mice with acute myocardial infarction may lead to metabolic disorder of fat factor, and Atto vastatin can improve the metabolic disorder of fat factor by anti-inflammatory effect.
【作者单位】：中南大学湘雅二医院心血管内科;中南大学湘雅二医院口腔科;
【基金】：国家自然科学基金(81000121)~~
【分类号】：R542.22

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