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基质金属蛋白酶及其在槲皮素对老年 Zucker 糖尿病脂肪大鼠心脏功能影响机制中的作用

Matrix Metalloproteinases and Their Role in Mechanisms Underlying Effects of Quercetin on Heart Function in Aged Zucker Diabetic Fatty Rats.

作者信息

Boťanská Barbora, Barteková Monika, Ferenczyová Kristína, Fogarassyová Mária, Kindernay Lucia, Barančík Miroslav

机构信息

Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Dúbravská Cesta 9, 841 04 Bratislava, Slovakia.

出版信息

Int J Mol Sci. 2021 Apr 24;22(9):4457. doi: 10.3390/ijms22094457.

DOI:10.3390/ijms22094457
PMID:33923282
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8123171/
Abstract

Several mechanisms may contribute to cardiovascular pathology associated with diabetes, including dysregulation of matrix metalloproteinases (MMPs). Quercetin (QCT) is a substance with preventive effects in treatment of cardiovascular diseases and diabetes. The aim of the present study was to explore effects of chronic QCT administration on changes in heart function in aged lean and obese Zucker Diabetic Fatty (ZDF) rats and that in association with MMPs. Signaling underlying effects of diabetes and QCT were also investigated. In the study, we used one-year-old lean and obese ZDF rats treated for 6 weeks with QCT. Results showed that obesity worsened heart function and this was associated with MMP-2 upregulation, MMP-28 downregulation, and inhibition of superoxide dismutases (SODs). Treatment with QCT did not modulate diabetes-induced changes in heart function and MMPs. However, QCT activated Akt kinase and reversed effects of diabetes on SODs inhibition. In conclusion, worsened heart function due to obesity involved changes in MMP-2 and MMP-28 and attenuation of antioxidant defense by SOD. QCT did not have positive effects on improvement of heart function or modulation of MMPs. Nevertheless, its application mediated activation of adaptive responses against oxidative stress through Akt kinase and prevention of diabetes-induced negative effects on antioxidant defense by SODs.

摘要

几种机制可能导致与糖尿病相关的心血管病变，包括基质金属蛋白酶（MMPs）的失调。槲皮素（QCT）是一种对心血管疾病和糖尿病治疗具有预防作用的物质。本研究的目的是探讨长期给予QCT对老年瘦型和肥胖型Zucker糖尿病脂肪大鼠（ZDF）心脏功能变化的影响，以及与MMPs的关系。还研究了糖尿病和QCT作用的潜在信号通路。在本研究中，我们使用了一岁的瘦型和肥胖型ZDF大鼠，用QCT治疗6周。结果表明，肥胖会使心脏功能恶化，这与MMP-2上调、MMP-28下调以及超氧化物歧化酶（SODs）的抑制有关。QCT治疗并未调节糖尿病引起的心脏功能和MMPs变化。然而，QCT激活了Akt激酶，并逆转了糖尿病对SODs抑制的作用。总之，肥胖导致的心脏功能恶化涉及MMP-2和MMP-28的变化以及SOD对抗氧化防御的减弱。QCT对改善心脏功能或调节MMPs没有积极作用。然而，其应用通过Akt激酶介导了对氧化应激的适应性反应的激活，并预防了糖尿病对SODs抗氧化防御的负面影响。

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