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首页> 外文期刊>Cellular Physiology and Biochemistry >Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats
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Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats

机译：芦荟大黄素可通过MiR-1抑制和IK1上调缓解高脂饮食诱导的QT延长。

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>Background/Aims: High-fat diet (HFD) causes cardiac electrical remodeling and increases the risk of ventricular arrhythmias. Aloe-emodin (AE) is an anthraquinone component isolated from rhubarb and has a similar chemical structure with emodin. The protective effect of emodin against cardiac diseases has been reported in the literature. However, the cardioprotective property of AE is still unknown. The present study investigated the effect of AE on HFD-induced QT prolongation in rats. Methods: Adult male Wistar rats were randomly divided into three groups: control, HFD, and AE-treatment groups. Normal diet was given to rats in the control group, high-fat diet was given to rats in HFD and AE-treatment groups for a total of 10 weeks. First, HFD rats and AE-treatment rats were fed with high-fat diet for 4 weeks to establish the HFD model. Serum total cholesterol and triglyceride levels were measured to validate the HFD model. Afterward, AE-treatment rats were intragastrically administered with 100 mg/kg AE each day for 6 weeks. Electrocardiogram monitoring and whole-cell patch-clamp technique were applied to examine cardiac electrical activity, action potential and inward rectifier K+ current (IK1), respectively. Neonatal rat ventricular myocytes (NRVMs) were subjected to cholesterol and/or AE. Protein expression of Kir2.1 was detected by Western blot and miR-1 level was examined by real-time PCR in vivo and in vitro, respectively. Results: In vivo, AE significantly shortened the QT interval, action potential duration at 90% repolarization (APD90) and resting membrane potential (RMP), which were markedly elongated by HFD. AE increased IK1 current and Kir2.1 protein expression which were reduced in HFD rats. Furthermore, AE significantly inhibited pro-arrhythmic miR-1 in the hearts of HFD rats. In vitro, AE decreased miR-1 expression levels resulting in an increase of Kir2.1 protein levels in cholesterol-enriched NRVMs. Conclusions: AE prevents HFD-induced QT prolongation by repressing miR-1 and upregulating its target Kir2.1. These findings suggest a novel pharmacological role of AE in HFD-induced cardiac electrical remodeling.
机译：> 背景/目标： 高脂饮食（HFD）会导致心脏电重构，并增加室性心律失常的风险。芦荟大黄素（AE）是从大黄中分离出的蒽醌成分，化学结构与大黄素相似。大黄素对心脏疾病的保护作用已有文献报道。然而，AE的心脏保护特性仍然未知。本研究调查了AE对HFD诱导的QT延长的影响。 方法： 将成年雄性Wistar大鼠随机分为三组：对照组，HFD和AE治疗组。对照组给予正常饮食，HFD和AE治疗组给予高脂饮食，共10周。首先，以高脂饮食喂养HFD大鼠和AE治疗大鼠4周，以建立HFD模型。测量血清总胆固醇和甘油三酸酯水平以验证HFD模型。此后，每天用100 mg / kg AE灌胃AE治疗的大鼠，持续6周。应用心电图监测和全细胞膜片钳技术分别检查心脏电活动，动作电位和内向整流子K + 电流（I K1 ）。新生大鼠心室肌细胞（NRVM）接受胆固醇和/或AE。通过Western blot检测Kir2.1的蛋白表达，并通过实时PCR分别在体内和体外检测miR-1水平。 结果： 体内AE显着缩短了QT间隔，复极化90％时动作电位持续时间（APD 90 ）和静息膜电位（RMP），这被HFD显着延长。 AE增加了HFD大鼠的I K1 电流和Kir2.1蛋白的表达，而AE降低了。此外，AE明显抑制了HFD大鼠心脏的心律失常前miR-1。 体外，AE降低了富含胆固醇的NRVM中miR-1的表达水平，导致Kir2.1蛋白水平升高。 结论： AE通过抑制miR-1并上调其目标Kir2.1来阻止HFD诱导的QT延长。这些发现表明AE在HFD诱导的心脏电重构中具有新的药理作用。

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