槲皮素通过 AMPK/mTOR 信号通路调节自噬和细胞凋亡改善糖尿病大鼠的心肌损伤

The American journal of Chinese medicine Pub Date : 2024-01-01 Epub Date: 2024-05-08 DOI:10.1142/S0192415X24500344
Yong-Feng Chen, Qi Qiu, Lei Wang, Xiao-Rong Li, Shun Zhou, Heng Wang, Wen-Di Jiang, Jia-Yi Geng, Qin-Gao, Bi Tang, Hong-Ju Wang, Pin-Fang Kang
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摘要

高糖环境与糖尿病(DM)的进展有关。本研究旨在探讨槲皮素(QUE)对DM大鼠心肌损伤后自噬和细胞凋亡的调节作用。研究采用低剂量链脲佐菌素(STZ)治疗结合高碳水化合物(HC)饮食的方法构建了2型DM大鼠模型。与对照组相比,糖尿病组的体重下降,而血压、血糖和左心室重量/体重比增加。结果显示,糖尿病组心肌纤维紊乱。此外,我们还发现与对照组相比,糖尿病组心肌胶原纤维、PAS 阳性细胞和细胞凋亡增加,而线粒体结构遭到破坏,自噬空泡明显减少。在体外和体内,糖尿病组自噬相关蛋白 LC3 和 Beclin1 的表达水平下降,而 P62、Caspae-3 和 Bax/Bcl-2 的表达水平升高。此外,QUE还能缓解高糖环境下的细胞氧化应激反应。免疫沉淀(IP)结果显示,自噬蛋白Beclin1与Bcl-2结合,且结合能力在HG组中增加,而QUE处理后降低,表明QUE抑制了Beclin1与Bcl-2的结合能力,从而导致Beclin1诱导的自噬得以保留。此外,QUE 治疗后大鼠的血压、血糖和心脏功能都得到了改善。总之,QUE通过AMPK/mTOR信号通路调节糖尿病心肌自噬和抑制心肌细胞凋亡,从而抑制糖尿病心肌损伤并改善心功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Quercetin Ameliorates Myocardial Injury in Diabetic Rats by Regulating Autophagy and Apoptosis through AMPK/mTOR Signaling Pathway.

A high-glucose environment is involved in the progression of diabetes mellitus (DM). This study aims to explore the regulatory effects of quercetin (QUE) on autophagy and apoptosis after myocardial injury in rats with DM. The type 2 DM rat models were constructed using low-dose streptozotocin (STZ) treatment combined with a high-carbohydrate (HC) diet in vivo. Compared with the control group, the body weight was decreased, whereas blood pressure, blood glucose, and the LVW/BW ratio were increased in the diabetic group. The results showed that the myocardial fibers were disordered in the diabetic group. Moreover, we found that the myocardial collagen fibers, PAS-positive cells, and apoptosis were increased, whereas the mitochondrial structure was destroyed and autophagic vacuoles were significantly reduced in the diabetic group compared with the control group. The expression levels of autophagy-related proteins LC3 and Beclin1 were decreased, whereas the expression levels of P62, Caspae-3, and Bax/Bcl-2 were increased in the diabetic group in vitro and in vivo. Moreover, QUE treatment alleviated the cellular oxidative stress reaction under high-glucose environments. The results of immunoprecipitation (IP) showed that the autophagy protein Beclin1 was bound to Bcl-2, and the binding capacity increased in the HG group, whereas it decreased after QUE treatment, suggesting that QUE inhibited the binding capacity between Beclin1 and Bcl-2, thus leading to the preservation of Beclin1-induced autophagy. In addition, the blood pressure, blood glucose, and cardiac function of rats were improved following QUE treatment. In conclusion, QUE suppressed diabetic myocardial injury and ameliorated cardiac function by regulating myocardial autophagy and inhibition of apoptosis in diabetes through the AMPK/mTOR signaling pathway.

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