Breviscapine ameliorates cardiac dysfunction and regulates the myocardial Ca(2+)-cycling proteins in streptozotocin-induced diabetic rats.
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 Ca(2+)-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 Ca(2+)-ATPase (SERCA-2), ryanodine receptor (RyR) were detected by western blot or RT-PCR. The activity of SERCA-2 was measured using Ca(2+)-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.
Wang
Min
M
Key Laboratory of Biotherapy of Zhejiang Province, Department of Cardiovascular Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, 310016, Hangzhou, Zhejiang Province, People's Republic of China. wangmin_hzzjusyf@yeah.net
Zhang
Wen-bin
WB
Zhu
Jun-hui
JH
Fu
Guo-sheng
GS
Zhou
Bin-quan
BQ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005419:Flavonoids / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D047908:Intracellular Signaling Peptides and Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C021042:protein phosphatase inhibitor-1; C061097:breviscapine