从ERS细胞凋亡信号通路探讨降糖舒心方对糖尿病心脏重塑影响的研究

项目名称： 从ERS细胞凋亡信号通路探讨降糖舒心方对糖尿病心脏重塑影响的研究

项目编号： No.81460698

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 符显昭

作者单位： 右江民族医学院

项目金额： 45万元

中文摘要： 糖尿病心脏病(DC)是糖尿病(DM)常见的并发症，是导致糖尿病患者死亡的主要原因。目前已明确，导致心力衰竭发生发展的基本机制是心脏重塑，因此如何防止和延缓心脏重塑的发展是目前研究的热点。心肌细胞凋亡在心脏重塑进展中起着重要作用，而内质网应激(ERS)是导致细胞凋亡的原因之一。DM的多种病理因素，均易诱发ERS，产生严重而持久的ERS，超过内质网自我修复能力，使PERK、ATF6 及IRE-1与BIP分离，激活下游的凋亡信号分子：CHOP、c-JNK、Caspase12，导致心肌细胞凋亡。中医理论认为DM属于消渴病范畴，气虚致瘀，阴虚致内热，热瘀内蕴可化毒，因此气阴两虚、瘀毒内蕴是DC的主要病机。降糖舒心方有益气养阴、活血解毒的功能。本课题在前期研究的基础上，从ERS细胞凋亡信号通路探讨降糖舒心方对DC作用，揭示其抑制心脏重塑的分子机制，为滋阴益气活血解毒对DC的治疗提供科学依据。

中文关键词： 糖尿病心脏病；内质网应激；心脏重构；细胞凋亡；降糖舒心方

英文摘要： Increasing morbidity and mortality have made heart failure (HF) become the most major cardiovascular disease of the 21 century in recent years. Diabetes mellitus is a world prevalent disease with increasing prevalence, followed with the rising number of the patients with coronary macrovascular disease, concomitant hypertension, microvascular complication, and cardiac autonomic neuropathy. It has been demonstrated now that the fundamental mechanisms responsible for the development and progression of HF is myocardial remodeling, which is defined as the changes of heart in structure, including the accumulation and altered composition of extracellular matrix(ECM). Myocardial remodeling is the common character, as a result of the development of various cardiac diseases. Cardiomyocyte apoptosis plays a critical role in myocardial remodeling, and endoplasmic reticulum stress (ERS) is one of intrinsic apoptosis pathways. The endoplasmic reticulum (ER) is a central organelle entrusted with lipid synthesis, calcium homeostasis, protein folding and maturation. Various factors, including oxidative stress, ischemia, disturbance of calcium homeostasis, and overexpression of incorrectly folded proteins, can interfere with ER function and lead to ERS. Multiple pathogenic factors of diabetes, such as hyperglycemia, hyperlipidemia, homocysteine(Hcy), Ang II, hypoxia and so on, can invoke ER stress and initiate the cardiac inflammation, which make a vicious cycle, and eventually lead to cell apoptosis and associated myocardial remodeling . Therefore, blocking endoplasmic reticulum stress-related cells apoptosis pathway can act as a potential approach for interrupting myocardial remodeling. 　 According to Traditional Chinese medicine（TCM）theory, diabetic myocardial remodeling is essentially belonged to the categories of Xiao Ke complicated with cardiopathy. Yin debilitation and Qi deficiency, Combined with dryness-heat, are the Xiao Ke cardiopathy basic constitution. With the development of the disease, heart Qi unable to promote the blood circulation, leading to Qi stagnation and blood stasis; Or the accumulation of internal heat damage body fluid, transform into fire and result in internal exuberance of fire-heat that may in turn consume or scorch the body Yin-fluids and blood, and subsequently lead to blood and fluid stasis and change into stasis toxin.Therefore, the co-existence of deficiency of both Qi and Yin, blood stasis and toxin accumulation is the important intrinsic pathogenesis of diabetic myocardial remodeling. The strategy of Supplementing Qi and Nourishing Yin, Activating blood circulation and Detoxifying（SNAD）is the basic method of treating diabetic myocardial remodeling.The purpose of this study is to explore the effect of JIANG TANG SUXI decoction，which possessing SNAD, confirm that SNAD may be one of the effective methods for the prevention and treatment of diabetic myocardial remodeling.

英文关键词： diabetic cardiovascular disease;endoplasmic reticulum stress;myocardial remodeling;apoptosis;Jiang Tang Shu Xin Decoction