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ABSTRACT: 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.
Acta Diabetologica 10/2009; 47(Suppl 1):209-18. · 2.78 Impact Factor
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ABSTRACT: To investigate the influence of breviscapine on high glucose-induced hypertrophy of cardiomyocytes and the relevant mechanism in vitro and in vivo.
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-kappaB inhibitor BAY11-7082. Cellular contraction frequency and volumes were measured; the expression of protein kinase C (PKC), NF-kappaB, TNF-alpha, 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 x kg(-1) x 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-kappaB, TNF-alpha, and c-fos were measured by Western blot or RT-PCR.
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-kappaB, TNF-alpha, 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-kappaB, TNF-alpha, and c-fos; treatment with breviscapine could ameliorate these changes in diabetic cardiomyopathy.
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-kappaB/c-fos signal transduction pathway.
Acta Pharmacologica Sinica 09/2009; 30(8):1081-91. · 1.95 Impact Factor
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ABSTRACT: The purpose of this study is to investigate the effect of chelerythrine on the hypertrophy of cardiomyocytes of neonatal rats induced by different glucose levels and its mechanism. Using cultured neonatal ventricular myocytes as a model, groups were divided as: control (5 mmol x L(-1)); high glucose level (10, 15, 20, and 25.5 mmol x L(-1)); high glucose level (25.5 mmol x L(-1)) add different concentrations of chelerythrine (1 and 8 micromol x L(-1)); and control glucose level (5 mmol x L(-1)) add different concentrations of chelerythrine (1 and 8 micromol x L(-1)). Different groups of cardiomyocytes after adding corresponding treat factors were cultured for 48 hours. Cardiomyocytes' diameters and protein level were measured and the expression of PKC-alpha, PKC-beta2, p-PKC-alpha, and p-PKC-beta2 were measured by Western blotting. Compared with control group, neonatal myocytes cultured in high glucose levels showed increased cellular volumes, protein level and expression of PKC-alpha, PKC-beta2, p-PKC-alpha, p-PKC-beta2. When chelerythrine was added, cellular volumes, protein level and expression of PKC-alpha, PKC-beta2, p-PKC-alpha, p-PKC-beta2 were significantly reduced. But in 1 micromol x L(-1) chelerythrine group, the expression of PKC-beta2 was not significantly reduced. The result suggested that chelerythrine can reverse the hypertrophy induced by different glucose levels on the cardiac myocytes, it may have protective effect against diabetic cardiomyopathy via PKC passageway.
Yao xue xue bao = Acta pharmaceutica Sinica 03/2009; 44(2):115-20.
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ABSTRACT: To study the influence of various glucose levels on the structure and function of cultured neonatal rats cardiomyocytes.
Cultured neonatal ventricular cardiomyocytes were treated with various glucose levels for 5 days: control (5.5 mmol/L); high (25.5 mmol/L); intermittent high (5.5 mmol/L or 25.5 mmol/L in every 12 hours interval); high (25.5 mmol/L) + PKC inhibitor Ro-31-8220 (50 nmol/L). Then, the cell beating frequency was counted, the cardiomyocytes diameters were measured and the expressions of PKC-alpha, PKC-beta(2), p-PKC-alpha, p-PKC-beta(2), NF-kappaB and c-fos were determined by Western blot.
Compared with control group, cardiomyocytes beating frequency, diameters as well as the expressions of PKC-alpha, PKC-beta(2), p-PKC-alpha, p-PKC-beta(2), NF-kappaB and c-fos were significantly increased in high glucose concentration (all P < 0.05) and intermittent high glucose treatment further amplified these changes (all P < 0.05 vs. high glucose and control groups). High glucose induced changes could be significantly attenuated with PKC inhibitor Ro-31-8220.
High, especially intermittent high glucose could lead to diabetic cardiomyopathy by promoting cardiac hypertrophy, increasing beating frequency via activating PKC/NF-kappaB/c-fos pathways.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 11/2008; 36(11):1027-31.
