Breviscapine ameliorates cardiac dysfunction and regulates the myocardial Ca2+-cycling proteins in streptozotocin-induced diabetic rats

被引:7
作者
Min Wang
Wen-bin Zhang
Jun-hui Zhu
Guo-sheng Fu
Bin-quan Zhou
机构
[1] Zhejiang University,Key Laboratory of Biotherapy of Zhejiang Province, Department of Cardiovascular Diseases, Sir Run Run Shaw Hospital, College of Medicine
来源
Acta Diabetologica | 2010年 / 47卷
关键词
Diabetic cardiomyopathy; Protein kinase C; Breviscapine;
D O I
暂无
中图分类号
学科分类号
摘要
To investigate the influence of breviscapine on the cardiac structure and function in diabetic cardiomyopathy rats as well as the expression of protein kinase C (PKC) and Ca2+-cycling proteins expression. Diabetes was induced in male Sprague–Dawley rats by a single intraperitoneal injection of streptozotocin and the control rats were injected with saline. After the induction of diabetes for 4 weeks, the animals were divided into different groups: (1) normal rats as control; (2) diabetic rats; (3) diabetic rats with administration of breviscapine (10 or 25 mg kg−1 day−2). After treatment with breviscapine for 6 weeks, the invasive cardiac function and echocardiographic parameters were measured, and heart tissue was obtained for electron microscope study. The expression of protein kinase C (PKC) and calcium handling regulators, such as protein phosphatase inhibitor-1 (PPI-1), phospholamban (PLB) and Ca2+-ATPase (SERCA-2), ryanodine receptor (RyR) were detected by western blot or RT-PCR. The activity of SERCA-2 was measured using Ca2+-ATPase kit. Diabetic rats showed impaired cardiac structure and function compared with control rats. The expression of PKC, PLB increased significantly, while the PPI-1, SERCA-2 and RyR expression decreased. Treatment with breviscapine could reverse the cardiac dysfunction and structure changes in diabetic cardiomyopathy rats, and decrease the expression of PKC and PLB, as well as increase the expression of PPI-1, SERCA-2 and RyR. The protective effect of breviscapine was dose related. This study showed that breviscapine could regulate the expression of PKC, PPI-1, PLB and SERCA-2 and have protective effect on diabetic cardiomyopathy.
引用
收藏
页码:209 / 218
页数:9
相关论文
共 226 条
[11]  
Akiyama N(2001)Protein kinase C and the development of diabetic vascular complications Diabet Med 18 945-959
[12]  
Hashimoto H(2000)Vascular dysfunction in hyperglycemia: is protein kinase C the culprit? Circ Res 9 5-7
[13]  
Ogawa K(2005)Protein kinase C isozymes in hypertension and hypertrophy: insight from SHHF rat hearts Mol Cell Biochem 270 63-69
[14]  
Satake T(2003)Regulation of protein kinase C isozyme and calcineurin expression in isoproterenol induced cardiac hypertrophy J Cardiovasc Pharmacol 41 946-954
[15]  
Brownlee M(2003)Differential induction of protein kinase C isoforms at the cardiac hypertrophy stage and congestive heart failure stage in Dahl salt-sensitive rats Hypertens Res 26 421-426
[16]  
Wold LE(2003)Upregulation of PKC genes and isozymes in cardiovascular tissues during early stages of experimental diabetes Physiol Genomics 12 139-146
[17]  
Dutta K(2006)Alterations in cardiac contractile performance and sarcoplasmic reticulum function in sucrose-fed rats is associated with insulin resistance Am J Physiol Cell Physiol 291 C772-C780
[18]  
Mason MM(2004)Decreased sarcoplasmic reticulum activity and contractility in diabetic db/db mouse heart Diabetes 53 3201-3208
[19]  
Ren J(2007)Transcoronary gene transfer of SERCA2a increases coronary blood flow and decreases cardiomyocyte size in a type 2 diabetic rat model Am J Physiol Heart Circ Physiol 292 H1204-H1207
[20]  
Cala SE(2006)Pharmacological- and gene therapy-based inhibition of protein kinase C alpha/beta enhances cardiac contractility and attenuates heart failure Circulation 114 574-582