Breviscapine ameliorates cardiac dysfunction and regulates the myocardial Ca2+-cycling proteins in streptozotocin-induced diabetic rats
Breviscapine ameliorates cardiac dysfunction and regulates the myocardial Ca2+-cycling proteins in streptozotocin-induced diabetic rats
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DOI：
10.1007/s00592-009-0164-x
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发表时间：
2010-12-01
影响因子：
3.8
通讯作者：
Zhou, Bin-quan
中科院分区：
文献类型：
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作者：
Wang, Min;Zhang, Wen-bin;Zhou, Bin-quan
目的：探讨灯盏花素对糖尿病心肌病大鼠心脏结构和功能的影响，以及对蛋白激酶C(PKC)和钙循环蛋白表达的影响。雄性SD大鼠一次性腹腔注射链脲佐菌素复制糖尿病模型，对照组注射生理盐水。造模4周后，动物分为正常对照组、糖尿病大鼠、灯盏花素灌胃组(10或25 mg·kg~(-1)·d~(-2))。灯盏花素治疗6周后，测量有创心功能和超声心动图参数，并取心脏组织作电镜观察。免疫印迹和RT-PCR检测蛋白激酶C(PKC)和钙调节因子蛋白磷酸酶抑制物-1(PPI-1)、磷蛋白(PLB)、钙离子-三磷酸腺苷酶(SERCA-2)、兰尼定受体(RyR)的表达。用Ca2+-ATPase试剂盒检测SERCA-2活性。与对照组相比，糖尿病大鼠心脏结构和功能受损。PKC、PLB表达明显增加，PPI-1、SERCA-2、RyR表达降低。灯盏花素可逆转糖尿病心肌病大鼠的心功能障碍和结构改变，降低PKC和PLB的表达，增加PPI-1、SERCA-2和RyR的表达。灯盏花素的保护作用与剂量相关。本研究表明灯盏花素可调节PKC、PPI-1、PLB和SERCA-2的表达，对糖尿病心肌病变具有保护作用。
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.