Treatment with crocin improves cardiac dysfunction by normalizing autophagy and inhibiting apoptosis in STZ-induced diabetic cardiomyopathy
Treatment with crocin improves cardiac dysfunction by normalizing autophagy and inhibiting apoptosis in STZ-induced diabetic cardiomyopathy
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DOI：
10.1016/j.numecd.2018.06.005
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发表时间：
2018-09-01
影响因子：
3.9
通讯作者：
Lazou, A.
中科院分区：
文献类型：
--
作者：
Feidantsis, K.;Mellidis, K.;Lazou, A.
背景和目标：糖尿病（DM）和代谢控制不良与心血管疾病的高发病率之间的关系已得到充分证实。本研究旨在探讨西红花苷（Crocus sativus L.）方法和结果：链脲佐菌素（STZ）诱导的糖尿病大鼠用两种不同浓度的藏红花素（10或20 mg/kg）处理，而暴露于25 mM葡萄糖的分离的心肌细胞用1或10 mM藏红花素处理。用藏红花素治疗STZ糖尿病大鼠可使血糖水平正常化，抑制心脏肥大和纤维化，并改善心脏收缩功能。热休克反应增强。西红花苷治疗后心肌AMPK磷酸化增加，导致自噬标志蛋白（LC 3BII/LC 3BI比值，SQSTM 1/p62和Beclin-1）正常化，而糖尿病诱导的心肌细胞凋亡减少。结论：西红花苷通过增强热休克反应、抑制心肌细胞凋亡、使心肌细胞自噬正常化，从而改善糖尿病大鼠心脏功能。因此，用藏红花素治疗可能代表治疗糖尿病性心肌病的新方法。(C)2018年意大利糖尿病学会，意大利动脉粥样硬化研究学会，意大利人类营养学会，以及Federico II大学临床医学和外科系。Elsevier B. V.出版，保留所有权利。
Background and aim: The association of diabetes mellitus (DM) and poor metabolic control with high incidence of cardiovascular diseases is well established. The aim of this study was to investigate the potential cardioprotective effect of crocin (Crocus sativus L. extract) on diabetic heart dysfunction and to elucidate the mediating molecular mechanisms.Methods and results: Streptozotocin (STZ)-induced diabetic rats were treated with two different concentrations of crocin (10 or 20 mg/kg), while isolated cardiac myocytes exposed to 25 mM glucose, were treated with 1 or 10 mM of crocin. Treatment of STZ-diabetic rats with crocin resulted in normalization of plasma glucose levels, inhibition of cardiac hypertrophy and fibrosis, and improvement of cardiac contractile function. Heat Shock Response was enhanced. Myocardial AMPK phosphorylation was increased after treatment with crocin, resulting in normalization of autophagy marker proteins (LC3BII/LC3BI ratio, SQSTM1/p62 and Beclin-1), while the diabetes-induced myocardial apoptosis was decreased. Similar results regarding the effect of crocin on autophagy and apoptosis pathways were obtained in isolated cardiac myocytes exposed to high concentration of glucose.Conclusion: The results suggest that crocin improves the deteriorated cardiac function in diabetic animals by enhancing the heat shock response, inhibiting apoptosis and normalizing autophagy in cardiac myocytes. Thus, treatment with crocin may represent a novel approach for treating diabetic cardiomyopathy. (C) 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.