阿托伐他汀改善急性心肌梗死小鼠炎癥誘導(dǎo)性脂肪因子代謝紊亂
發(fā)布時間:2018-05-09 07:52
本文選題:急性心肌梗死 + 動脈粥樣硬化; 參考:《中南大學(xué)學(xué)報(bào)(醫(yī)學(xué)版)》2017年07期
【摘要】:目的:明確急性心肌梗死(acute myocardial infarction,AMI)期間炎癥激活與脂肪因子代謝紊亂的關(guān)系,探討阿托伐他汀的潛在治療作用及其機(jī)制。方法:32只C57BL/6小鼠隨機(jī)分為4組:假手術(shù)組、AMI組、小劑量阿托伐他汀組[2 mg/(kg.d)]和大劑量阿托伐他汀組[20 mg/(kg.d)]。干預(yù)3周后,后3組采用冠狀動脈結(jié)扎術(shù)構(gòu)建AMI模型,測定小鼠血漿高敏C反應(yīng)蛋白(high sensitive C reaction protein,hs-CRP)濃度,以及血漿和組織中脂聯(lián)素和抵抗素的表達(dá)。體外誘導(dǎo)小鼠3T3L1前脂肪細(xì)胞分化成熟后,觀察氧化低密度脂蛋白(oxidized low density lipoprotein,ox-LDL)對細(xì)胞脂聯(lián)素和抵抗素表達(dá)的影響,并研究不同劑量阿托伐他汀干預(yù)對ox-LDL所致脂肪因子代謝紊亂的作用。結(jié)果:動物實(shí)驗(yàn)顯示AMI小鼠血漿hs-CRP和抵抗素濃度均明顯升高,而脂聯(lián)素明顯降低。阿托伐他汀預(yù)處理呈劑量依賴性抑制AMI小鼠血漿上述因子濃度變化。hs-CRP和抵抗素在小鼠脂肪組織中表達(dá)也觀察到類似的結(jié)果。相關(guān)性分析顯示血漿hsCRP濃度與抵抗素呈正相關(guān),而與脂聯(lián)素呈負(fù)相關(guān)。體外試驗(yàn)顯示ox-LDL刺激可上調(diào)脂肪細(xì)胞抵抗素表達(dá),同時降低脂聯(lián)素表達(dá),而阿托伐他汀呈劑量依賴性逆轉(zhuǎn)上述ox-LDL效應(yīng)。結(jié)論:AMI小鼠體內(nèi)炎癥激活導(dǎo)致脂肪因子代謝紊亂,而阿托伐他汀通過抗炎作用可改善此類脂肪因子代謝紊亂。
[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.
【作者單位】: 中南大學(xué)湘雅二醫(yī)院心血管內(nèi)科;中南大學(xué)湘雅二醫(yī)院口腔科;
【基金】:國家自然科學(xué)基金(81000121)~~
【分類號】:R542.22
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