| 引用本文:王瑞1，高钊2，张晓东2，樊贝贝2，孙梦娜2，王伟2，曾广伟2.白藜芦醇通过调节沉默信息调节因子1通路改善大鼠心肌缺血再灌注损伤的作用机制[J].世界中医药,2022,(15):. |
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| 白藜芦醇通过调节沉默信息调节因子1通路改善大鼠心肌缺血再灌注损伤的作用机制 |
| Mechanism of Resveratrol Improving Myocardial Ischemia-Reperfusion Injury by Regulating Sirt1 Pathway in Rats |
| 投稿时间：2020-10-27 |
| DOI：10.3969/j.issn.1673-7202.2022.15.014 |
| 中文关键词: 白藜芦醇 心肌缺血再灌注 沉默信息调节因子1 核因子κB 炎症反应 心肌细胞 线粒体 |
| English Keywords:Resveratrol Myocardial ischemia-reperfusion Silent information regulatory factor-1(Sirt1) Nuclear factor kappa B Inflammatory response Cardiomyocytes Mitochondria |
| 基金项目:陕西省重点研发计划项目(2018SF-085) |
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| 中文摘要: |
| 目的:研究白藜芦醇(Res)对心肌缺血再灌注(MI/R)大鼠的改善作用,并初步探讨其通过调控沉默信息调节因子1（Sirt1）信号通路的作用机制。方法:将60只大鼠按照随机数字表法随机分为假手术组、心肌缺血再灌注模型组(MI/R组)、白藜芦醇组(Res组)和Sirt1抑制剂EX527组(EX527组),每组15只。检测各组大鼠心功能指标,酶联免疫吸附试验法检测肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平,采用比色法检测髓过氧化物酶(MPO)活力;蛋白质印迹法检测Sirt1和核因子κB蛋白表达水平。大鼠心肌细胞H9c2分为5组:对照组、缺氧/复氧组、Res组(缺氧/复氧+20 mmol/L Res处理)和EX527组(缺氧/复氧+1 μmol/L EX527处理)。采用四甲基偶氮唑盐(MTT)法检测各组细胞活力,Rhod-2 AM标记法检测线粒体钙离子浓度,钙黄绿素AM标记法检测线粒体通透性转换孔开放程度。结果:与MI/R组比较,Res组大鼠的左心室舒张末期压(LVEDP)、心肌损伤标志物、心肌梗死面积、炎症反应、核因子κB水平、MPO活力均明显降低(P<005),左心室收缩压（LVSP）、+dp/dtmm、-dp/dtmm和Sirt1水平均明显升高(P<005),而Sirt1抑制剂EX527可逆转Res对MI/R大鼠的改善作用(P<005)。与缺氧/复氧组比较,Res组的细胞活力和钙黄绿素相对荧光强度明显升高,而Rhod-2相对荧光强度明显下降(P<005)。与Res组比较,EX527组的细胞活力和钙黄绿素相对荧光强度明显下降,而Rhod-2相对荧光强度明显升高(P<005)。结论:白藜芦醇可明显改善大鼠心肌缺血再灌注损伤,并抑制缺氧/复氧诱导的心肌细胞线粒体钙超载和线粒体通透性转换孔过度开放。其机制可能与调控Sirt1信号通路有关。 |
| English Summary: |
| To analyze the effect of resveratrol(Res) on myocardial ischemia-reperfusion(MI/R) injury in rats，and to explore its mechanism by regulating Silent information regulatory factor-1(Sirt1) signaling pathway.Methods:A total of 60 rats were randomly divided into sham operation(sham) group，MI/R model group，Res group，and Sirt1 inhibitor EX527 group(EX527)，15 rats in each group.Electrocardiogram was used to detect the heart function indexes of rats in each group.The levels of creatine kinase-MB(CK-MB)，lactate dehydrogenase(LDH)，tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were detected by enzyme-linked immunosorbent assay(ELISA)，and the myeloperoxidase(MPO) activity was tested by colorimetric method.The protein expression levels of Sirt1 and NF-κB were determined by Western blot.Rat H9c2 cardiomyocytes were divided into 5 groups:control group，hypoxia/reoxygenation group(H/R)，Res group(H/R+20 mmol/L Res treatment) and EX527 group(H/R+1 μmol/L EX527 treatment).The cell viability was detected by MTT method.The mitochondrial calcium ion concentration and the openness of mitochondrial permeability transition pore(mPTP) were detected by Rhod-2 AM and by Calcein AM，respectively.Results:Compared with the conditions in MI/R group，the left ventricular end diastolic pressure(LVEDP)，markers of myocardial injury，infarct area，inflammatory response，protein expression level of NF-κB and MPO activity in Res group were reduced(P<005); the left ventricular systolic pressure(LVSP),+dp/dtmm,-dp/dtmm，and the protein expression level of Sirt1 were increased(P<005); while Sirt1 inhibitor EX527 reversed the improvement of Res in MI/R rats(P<005).Compared with the conditions in H/R group，the cell viability and the relative fluorescence intensity of Calcein in Res group were elevated，while the relative fluorescence intensity of Rhod-2 was decreased(P<005).Compared with Res group，the EX527 group had decreased cell viability but increased relative fluorescence intensity of Calcein(P<005).Conclusion:Resveratrol could significantly improve the MI/R injury in rats，and inhibit mitochondrial calcium overload and mPTP over-opening induced by H/R.The mechanism might be related to the regulation of Sirt1 signaling pathway. |
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