Abstract
Aim:
To investigate the influence of breviscapine on high glucose-induced hypertrophy of cardiomyocytes and the relevant mechanism in vitro and in vivo.
Methods:
Cultured neonatal cardiomyocytes were divided into i) control; ii) high glucose concentrations; iii) high glucose+PKC inhibitor Ro-31-8220; iv) high glucose+breviscapine; or v) high glucose+NF-κB inhibitor BAY11–7082. Cellular contraction frequency and volumes were measured; the expression of protein kinase C (PKC), NF-κB, TNF-α, and c-fos were assessed by Western blot or reverse transcription-polymerase chain reaction (RT-PCR). Diabetic rats were induced by a single intraperitoneal injection of streptozotocin, and randomly divided into i) control rats; ii) diabetic rats; or iii) diabetic rats administered with breviscapine (10 or 25 mg·kg−1·d−1). After treatment with breviscapine for six weeks, the echocardiographic parameters were measured. All rats were then sacrificed and heart tissue was obtained for microscopy. The expression patterns of PKC, NF-κB, TNF-α, and c-fos were measured by Western blot or RT-PCR.
Results:
Cardiomyocytes cultured in a high concentration of glucose showed an increased pulsatile frequency and cellular volume, as well as a higher expression of PKC, NF-κB, TNF-α, and c-fos compared with the control group. Breviscapine could partly prevent these changes. Diabetic rats showed relative cardiac hypertrophy and a higher expression of PKC, NF-κB, TNF-α, and c-fos; treatment with breviscapine could ameliorate these changes in diabetic cardiomyopathy.
Conclusion:
Breviscapine prevented cardiac hypertrophy in diabetic rats by inhibiting the expression of PKC, which may have a protective effect in the pathogenesis of diabetic cardiomyopathy via the PKC/NF-κB/c-fos signal transduction pathway.
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Acknowledgements
We thank the Department of Cardiovascular Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University for the use of test instruments and equipment.
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Wang, M., Zhang, Wb., Zhu, Jh. et al. Breviscapine ameliorates hypertrophy of cardiomyocytes induced by high glucose in diabetic rats via the PKC signaling pathway. Acta Pharmacol Sin 30, 1081–1091 (2009). https://doi.org/10.1038/aps.2009.95
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DOI: https://doi.org/10.1038/aps.2009.95
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