摘要
缺血导致的心肌细胞缺氧是缺血性心脏病的主要病理因素,糖尿病是缺血性心脏病最常见的合并症之一.冠心病合并糖尿病患者心肌损伤明显加重,预后差,可能与缺氧诱导因子1(hypoxia-inducible factor1,HIF-1)表达减少有关.但糖尿病时HIF-1信号转导系统改变的机制目前尚不清楚.近年来的研究表明,提高HIF-1α在缺血心肌中的表达及活性能明显促进新生血管形成,促进心肌细胞存活,减少缺血再灌注损伤,降低心肌梗塞面积,提高心肌功能,因此,调节HIF-1α的表达及活性成为治疗缺血性心脏病的新方法.通过制作GK糖尿病大鼠心肌梗塞模型,应用免疫组织化学染色、RT-PCR等方法研究发现,GK糖尿病大鼠合并心肌梗塞时,HIF-1α表达减少,心梗面积增大,而给予糖尿病大鼠慢性氯化钴处理后,其血糖水平降低,HIF-1α表达增加,心梗面积减小,这为如何调节HIF-1信号转导系统治疗冠心病合并糖尿病提供一个可能的新的治疗视点和策略.
Cardiomyocytes hypoxia resulting from ischemia is a major pathological factor in ischemic heart disease（IHD）, and diabetes is one of the most common complications in IHD. myocardial damages aggravate and prognosis is worse in patients with coronary heart disease and diabetes, which is probably concerned with the reduction of hypoxia-inducible factor 1 （HIF-1） expression. But the mechanisms of HIF-1 signal transduction system in diabetes are not clear. In recent years, many studies have indicated that increasing expression and activity of HIF-1α in IHD can promote neovascularization and cardiomyocytes survival, decrease ischemical reperfusion injury and myocardial infarction （MI） size, and increase myocardial function. Therefore regulating expression and activity of HIF-1α becomes a new way to treat IHD. Myocardial infarction models were made in GK diabetes rats through the ligation of left anterior descending coronary artery （LADCA）. By using immunohistochemistry staining and RT-PCR methods, results suggested that HIF-1α expression decreased and myocardial infarction size increased in GK diabetes rats combined with MI. When treated with cobalt chloride（CoCl2）, blood glucose level decreased, HIF-1α expression increased and myocardial infarction size reduced in GK diabetes rats, which may provide a new insight on treatment of coronary heart disease combined with diabetes by regulating HIF-1 signal transduction system.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2008年第6期712-718,共7页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金资助项目(30500212).~~
关键词
氯化钴
缺氧诱导因子1Α
糖尿病大鼠
心梗面积
血糖
cobalt chloride, hypoxia-inducible factor 1α, diabetes rats, myocardial infarction size, blood glucose
