Breviscapine ameliorates hypertrophy of cardiomyocytes induced by high glucose in diabetic rats via the PKC signaling pathway

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 inhibior Ro-31-8220; iv） high glucose＋breviscapine; or v） high glucose＋NF-KB inhibitor BAY11-7082. Cellular contraction frequency and volumes were measured; the expression of protein kinase C （PKC）, NF-KB, 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^-l.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-KB, 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-kB, TNF-α, and c-los compared with the control group. Breviscapine could partly prevent these changes. Diabetic rats showed relative cardiac hypertrophy and a higher expression of PKC, NF-KB, 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-kB/c-fos signal transduction pathway.