Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Heping West Road No. 215, Shijiazhuang, 050000, China.
Department of Cardiology, Shijiazhuang Great Wall Hospital of Integrated Traditional Chinese and Western Medicine, Shijiazhuang, 050000, China.
Cardiovasc Diabetol. 2022 Oct 11;21(1):205. doi: 10.1186/s12933-022-01643-0.
Diabetic cardiomyopathy is characterized by left ventricle dysfunction, cardiomyocyte apoptosis, and interstitial fibrosis and is a serious complication of diabetes mellitus (DM). Autophagy is a mechanism that is essential for maintaining normal heart morphology and function, and its dysregulation can produce pathological effects on diabetic hearts. Neuregulin-4 (Nrg4) is an adipokine that exerts protective effects against metabolic disorders and insulin resistance. The aim of this study was to explore whether Nrg4 could ameliorate DM-induced myocardial injury by regulating autophagy.
Four weeks after the establishment of a model of type 1 diabetes in mice, the mice received Nrg4 treatment (with or without an autophagy inhibitor) for another 4 weeks. The cardiac functions, histological structures and cardiomyocyte apoptosis were investigated. Autophagy-related protein levels along with related signalling pathways that regulate autophagy were evaluated. In addition, the effects of Nrg4 on autophagy were also determined in cultured primary cardiomyocytes.
Nrg4 alleviated myocardial injury both in vivo and in vitro. The autophagy level was decreased in type 1 diabetic mice, and Nrg4 intervention reactivated autophagy. Furthermore, Nrg4 intervention was found to activate autophagy via the AMPK/mTOR signalling pathway. Moreover, when autophagy was suppressed or the AMPK/mTOR pathway was inhibited, the beneficial effects of Nrg4 were diminished.
Nrg4 intervention attenuated diabetic cardiomyopathy by promoting autophagy in type 1 diabetic mice. Additionally, Nrg4 induced autophagy via the AMPK/mTOR signalling pathway.
糖尿病心肌病的特征是左心室功能障碍、心肌细胞凋亡和间质纤维化，是糖尿病（DM）的严重并发症。自噬是维持正常心脏形态和功能所必需的机制，其失调会对糖尿病心脏产生病理影响。神经调节蛋白 4（Nrg4）是一种脂肪细胞因子，对代谢紊乱和胰岛素抵抗具有保护作用。本研究旨在探讨 Nrg4 是否通过调节自噬来改善 DM 引起的心肌损伤。
在建立 1 型糖尿病小鼠模型 4 周后，小鼠接受 Nrg4 治疗（有或没有自噬抑制剂）4 周。研究了心脏功能、组织学结构和心肌细胞凋亡。评估了自噬相关蛋白水平以及调节自噬的相关信号通路。此外，还在原代心肌细胞中确定了 Nrg4 对自噬的影响。
Nrg4 体内和体外均减轻了心肌损伤。1 型糖尿病小鼠的自噬水平降低，Nrg4 干预重新激活了自噬。此外，发现 Nrg4 通过 AMPK/mTOR 信号通路干预自噬。此外，当自噬受到抑制或 AMPK/mTOR 通路被抑制时，Nrg4 的有益作用减弱。
Nrg4 通过促进 1 型糖尿病小鼠的自噬来减轻糖尿病心肌病。此外，Nrg4 通过 AMPK/mTOR 信号通路诱导自噬。
