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曲克芦丁对糖尿病心肌缺血/再灌注损伤的抗心律失常和抗炎作用。

Anti-arrhythmogenic and anti-inflammatory effects of troxerutin in ischemia/reperfusion injury of diabetic myocardium.

机构信息

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Biomed Pharmacother. 2018 Jun;102:385-391. doi: 10.1016/j.biopha.2018.03.047. Epub 2018 Mar 22.

Abstract

INTRODUCTION

Medicinal plants are increasingly used in the treatment of cardiovascular diseases due to their multifaceted properties. This study was designed to investigate anti-arrhythmic and anti-inflammatory potentials of the natural bioflavonoid, troxerutin (TXR) in myocardial ischemia/reperfusion (I/R) injury in diabetic rats.

METHODS

Male Wistar rats were randomly divided into 4 groups (control, control + TXR [150 mg/kg, daily], diabetic, and diabetic + TXR). Type-1 diabetes was induced by an intraperitoneal injection of streptozotocin (50 mg/kg) and lasted for 10 weeks. After mounting on the Langendorff apparatus, isolated hearts in all groups received a normal Krebs-Henseleit solution for 20 min of stabilization period, followed by 30 min of regional ischemia through ligation of the left anterior descending coronary artery, and 60 min of full reperfusion. During the experiment, the electrocardiograms were recorded and the arrhythmias [number, duration and incidence of premature ventricular complexes (PVC), ventricular tachycardia (VT), ventricular fibrillation (VF), and arrhythmia score] during I/R phases were assessed based on the Lambeth Convention. Ischemic left ventricular samples were used to determine the activities of lactate dehydrogenase (LDH), interleukin-1beta (IL-1β), and tumor necrosis factor (TNF-α).

RESULTS

The arrhythmias induced by I/R were not significantly changed in diabetic group as compared to the control group. However, pretreatment with TXR significantly reduced the number of PVC and duration and incidence of VF in ischemic phase in comparison to the untreated animals (P < 0.05). In addition, the duration, and incidence of most arrhythmias during reperfusion phase were significantly declined by TXR administration in both control and diabetic groups (P < 0.05). Pretreatment of rats with TXR significantly reduced myocardial inflammatory cytokines TNF-α and IL-1β levels after I/R insult in diabetic as well as control hearts (P < 0.05).

CONCLUSION

Preconditioning with TXR could provide cardioprotection by anti-arrhythmic and anti-inflammatory effects against I/R injury in rat hearts. This effect of TXR can introduce this material as a protective agent in cardiovascular diseases.

摘要

简介

由于具有多方面的特性,药用植物在治疗心血管疾病方面的应用日益广泛。本研究旨在探讨天然生物类黄酮曲克芦丁(TXR)在糖尿病大鼠心肌缺血/再灌注(I/R)损伤中的抗心律失常和抗炎潜力。

方法

雄性 Wistar 大鼠随机分为 4 组(对照组、对照组+TXR[150mg/kg,每日]、糖尿病组和糖尿病+TXR)。通过腹腔注射链脲佐菌素(50mg/kg)诱导 1 型糖尿病,持续 10 周。在 Langendorff 装置上安装后,所有组别的分离心脏均接受正常 Krebs-Henseleit 溶液 20min 的稳定期,随后通过结扎左前降支冠状动脉进行 30min 的区域缺血,以及 60min 的完全再灌注。在实验过程中,记录心电图,并根据兰伯特定律评估 I/R 期间的心律失常[数量、室性早搏(PVC)、室性心动过速(VT)、心室颤动(VF)的持续时间和发生率以及心律失常评分]。缺血左心室样本用于测定乳酸脱氢酶(LDH)、白细胞介素-1β(IL-1β)和肿瘤坏死因子(TNF-α)的活性。

结果

与对照组相比,糖尿病组的 I/R 诱导的心律失常没有明显变化。然而,与未治疗的动物相比,TXR 预处理可显著减少缺血期的 PVC 数量和 VT 的持续时间和发生率(P<0.05)。此外,在对照和糖尿病组中,TXR 给药可显著降低再灌注期大多数心律失常的持续时间和发生率(P<0.05)。TXR 预处理可显著降低糖尿病和对照组心脏 I/R 损伤后的心肌炎症细胞因子 TNF-α和 IL-1β水平(P<0.05)。

结论

TXR 的预处理可通过抗心律失常和抗炎作用提供对大鼠心脏 I/R 损伤的心脏保护作用。TXR 的这种作用可将该物质作为心血管疾病的保护剂。

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