姜黄素增强 1 型糖尿病实验模型中美汀的心脏保护作用;Nrf2/HO-1 和 JAK/STAT 通路的影响。

Curcumin augments the cardioprotective effect of metformin in an experimental model of type I diabetes mellitus; Impact of Nrf2/HO-1 and JAK/STAT pathways.

机构信息

Pharmacology and Toxicology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.

Pharmacology and Toxicology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.

出版信息

Biomed Pharmacother. 2019 Jan;109:2136-2144. doi: 10.1016/j.biopha.2018.11.064. Epub 2018 Nov 27.

Abstract

Metformin is one of the most commonly prescribed antidiabetic drugs. A recent clinical study has highlighted the protective role of metformin against cardiac complications in type I diabetes. Curcumin is a natural compound with well-known antioxidant and anti-inflammatory properties. The present study was designed to investigate the possible role of curcumin in potentiating metformin`s putative effects. Rats received single injection of 52.5 mg/kg streptozocin and the diabetic rats were treated with metformin (200 mg/kg/day), curcumin (100 mg/kg/day) and their combination for 6 weeks. Diabetic rats showed degenerated myocardium as well as significant increase in Creatine Kinase-MB (CK-MB), troponin I and TGF-β levels. In addition, cardiac levels of lipid peroxidation, IL-6, and NF-κB were significantly elevated. Although treatment with metformin restored most of the measured parameters, it showed insignificant improvement in histopathological architecture accompanied by absence of antioxidant effect. Interestingly, concomitant administration of curcumin along with metformin revealed more protection than metformin alone. Inhibition of JAK/STAT pathway and activation of Nrf2/HO-1 pathway seems to be among the mechanisms mediating the effects of curcumin and metformin. The findings of this study highlight the benefits of metformin/curcumin combination in preventing diabetic cardiomyopathy.

摘要

二甲双胍是最常用的抗糖尿病药物之一。最近的一项临床研究强调了二甲双胍在预防 1 型糖尿病心脏并发症方面的保护作用。姜黄素是一种具有已知抗氧化和抗炎特性的天然化合物。本研究旨在探讨姜黄素增强二甲双胍潜在作用的可能机制。大鼠接受单次注射 52.5mg/kg 链脲佐菌素,糖尿病大鼠用二甲双胍(200mg/kg/天)、姜黄素(100mg/kg/天)及其组合治疗 6 周。糖尿病大鼠的心肌出现退行性变,肌酸激酶同工酶-MB(CK-MB)、肌钙蛋白 I 和 TGF-β水平显著升高。此外,心脏脂质过氧化、IL-6 和 NF-κB 水平也显著升高。虽然二甲双胍治疗恢复了大多数测量参数,但对伴有抗氧化作用缺失的组织病理学结构的改善不明显。有趣的是,与单独使用二甲双胍相比,同时给予姜黄素和二甲双胍显示出更多的保护作用。抑制 JAK/STAT 通路和激活 Nrf2/HO-1 通路可能是姜黄素和二甲双胍作用的机制之一。本研究的结果强调了二甲双胍/姜黄素联合治疗预防糖尿病心肌病的益处。

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