Melatonin Ameliorates MI-Induced Cardiac Remodeling and Apoptosis through a JNK/p53-Dependent Mechanism in Diabetes Mellitus
Melatonin Ameliorates MI-Induced Cardiac Remodeling and Apoptosis through a JNK/p53-Dependent Mechanism in Diabetes Mellitus
复制标题
褪黑素通过 JNK p53 依赖性机制改善糖尿病中 MI 诱导的心脏重塑和细胞凋亡
DOI：
10.1155/2020/1535201
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发表时间：
2020-01-09
影响因子：
--
通讯作者：
Yang, Jian
中科院分区：
文献类型：
--
作者：
Lu, Linhe;Ma, Jipeng;Yang, Jian
糖尿病是一种全球性的健康威胁，被认为是心血管疾病的独立危险因素。糖尿病的总体心血管风险类似于一次心肌梗死（MI）发作，尽管糖尿病对MI诱导的心肌异常的确切影响仍然难以捉摸。鉴于糖尿病患者MI后的死亡率远高于非糖尿病患者，本研究旨在研究褪黑激素对糖尿病患者MI损伤诱导的心肌功能障碍的影响。在MI之前使用高脂肪喂养和链脲佐菌素（100 mg/kg体重）使成年小鼠患糖尿病，并在MI后用褪黑激素（50 mg/kg/d，p.o.）在评估心脏几何结构和功能之前持续4周。糖尿病患者的MI过程显示心脏几何结构（腔室扩张和间质纤维化）和功能异常（缩短分数和心肌细胞收缩能力降低）的明显变化，与c-Jun N-末端激酶（JNK）磷酸化和p53水平升高相关。褪黑激素治疗显着减轻心肌梗死后糖尿病小鼠的心功能不全和心肌纤维化。此外，褪黑激素降低JNK磷酸化，降低p53水平，并抑制心肌梗死后糖尿病组的心脏细胞凋亡。体外研究结果表明，褪黑素有效地抵消高糖/高脂缺氧诱导的心肌细胞凋亡和收缩功能障碍，通过JNK介导的机制，JNK激活剂茴香霉素的影响。总之，我们的研究表明，褪黑激素保护心肌梗死后糖尿病小鼠的心肌损伤，这为糖尿病心肌梗死诱导的心脏损伤的管理提供了一种新的治疗策略。
Diabetes mellitus, a worldwide health threat, is considered an independent risk factor for cardiovascular diseases. The overall cardiovascular risk of diabetes is similar to the one having one myocardial infarction (MI) attack although the precise impact of diabetes on MI-induced myocardial anomalies remains elusive. Given that mortality following MI is much greater in diabetic patients compared to nondiabetic patients, this study was designed to examine the effect of melatonin on MI injury-induced myocardial dysfunction in diabetes. Adult mice were made diabetic using high-fat feeding and streptozotocin (100 mg/kg body weight) prior to MI and were treated with melatonin (50 mg/kg/d, p.o.) for 4 weeks prior to assessment of cardiac geometry and function. The MI procedure in diabetes displayed overt changes in cardiac geometry (chamber dilation and interstitial fibrosis) and functional anomalies (reduced fractional shortening and cardiomyocyte contractile capacity) in association with elevated c-Jun N-terminal kinase (JNK) phosphorylation and p53 level. Melatonin treatment markedly attenuated cardiac dysfunction and myocardial fibrosis in post-MI diabetic mice. Furthermore, melatonin decreased JNK phosphorylation, reduced p53 levels, and suppressed apoptosis in hearts from the post-MI diabetic group. In vitro findings revealed that melatonin effectively counteracted high-glucose/high fat-hypoxia-induced cardiomyocyte apoptosis and contractile dysfunction through a JNK-mediated mechanism, the effects of which were impaired by the JNK activator anisomycin. In summary, our study suggests that melatonin protects against myocardial injury in post-MI mice with diabetes, which offers a new therapeutic strategy for the management of MI-induced cardiac injury in diabetes.