Objective To study the effects of simvastatin on the hypertrophy of cultured rat cardiac myocytes induced by serum and the role ofphosphatase and tensin homolog deleted on chromosome ten （PTEN） in the signal pathway...Objective To study the effects of simvastatin on the hypertrophy of cultured rat cardiac myocytes induced by serum and the role ofphosphatase and tensin homolog deleted on chromosome ten （PTEN） in the signal pathway. Methods Cultured neonatal Sprague- Dawley （SD） rat cardiac myocytes were treated with 15% fetal bovine serum, or without serum, or different consentrations of simvastatin. Image analysis system was used to measure the cardiac myocytes surface area. Protein synthesis of myocytes was measured via [3H]-leucine incorporation method. The expression level of atrial natriuretic peptide （ANP） mRNA in myocytes was determined with reverse transcription polymerase chain reaction （RT-PCR）. The mRNA and protein expression levels of PTEN in cardiac myocytes were investigated with RT-PCR and Western blot respectively. Results At 24 hours, cardiac myocytes surface area was significantly higher in 15% serum group （1611.16± 160.75 lam2） than in serum-free group （538.04±118.60 ±tm2, P〈0.01）. Simvastatin decreased the cell surface area in a concentration dependent manner. The cell surface area in 10-5 and 10-6 mol/L simvastatin groups were 799.84＋ 167.70 ±tm2 and 1076.88± 199.28 um2 respectively, which were both significantly lower than that in 15% fetal bovine serum group （P〈0.01）. Incorporation rate of [3H]-leucine was significantly higher in 15% fetal bovine serum group （2360± 106cpm/well） than that in serum-free group （1305±92 cpm/well, P〈0.01）. Incorporation rate of [3H]-leucine in 10.5 and 10.6 mol/L simvastatin groups were 1707±101 clam/well and 1962±125 cpm/well respectively, which were both lower than that in serum group （P〈0.01）. With the increase of simvastatin concentration, the expression level ofANP mRNA in cardiac myocytes was decreased gradually, which were 0.29±0.03 and 0.40-±0.03 respectively in 10.5 and 10-6 mol/L simvastatin groups, and significantly lower than that in serum group（0.60-±.03, P〈0.01）. Simvastatin increased the expressions of PTEN mRNA and protein in cardiac myocytes in a concentration dependent manner. PTEN mRNA expression level in 10-7, 10-6and 105mol/L simvastatin groups were 0.38±0.03, 0.83±0.04 and 0.85±0.05, respectively, which were all higher than that in 15% fetal bovine serum group （0.29±0.04, P〈0.05）. Similarly, PTEN protein level in 10-7, 10-6 and 10.5 mol/L simvastatin groups （39.25±3.41, 46.35±1.78 and 47.22±2.39 respectively） were also significantly higher than that in 15% fetal bovine serum group （32.21±4.06, P〈0.05）. Conclusion Simvastatin can inhibit the hypertrophy of cultured rat cardiac myoeytes induced by serum, and the increase of expression level of PTEN might be involved in the mechanism （J Geriatr Cardio12010; 7：47-51）.展开更多
Objective:Cardiac hypertrophy is an adaptive reaction of the heart against cardiac overloading,but continuous cardiac hypertrophy can lead to cardiac remodeling and heart failure.Cardiac hypertrophy is mostly consider...Objective:Cardiac hypertrophy is an adaptive reaction of the heart against cardiac overloading,but continuous cardiac hypertrophy can lead to cardiac remodeling and heart failure.Cardiac hypertrophy is mostly considered reversible,and recent studies have indicated that decorin not only prevents cardiac fibrosis associated with hypertension,but also achieves therapeutic effects by blocking fibrosis-related signaling pathways.However,the mechanism of action of decorin remains unknown and unconfirmed.Methods:We determined the degree of myocardial hypertrophy by measuring the ratios of the heart weight/body weight and left ventricular weight/body weight,histological analysis and immunohistochemistry.Western blotting was performed to detect the expression levels of CaMKⅡ,p-CaMKⅡ and MEF-2 in the heart.Results:Our results confirmed that decorin can regulate the CaMKⅡ/MEF-2 signaling pathway,with inhibition thereof being similar to that of decorin in reducing cardiac hypertrophy.Conclusion:Taken together,the results of the present study showed that decorin induced cardiac hypertrophy by regulating the CaMKⅡ/MEF-2 signaling pathway in vivo,revealing a new therapeutic approach for the prevention of cardiac hypertrophy.展开更多
Objective： To investigate the effects of sodium tanshinone Ⅱ A sulfonate （STS） on the hypertrophy induced by angiotensin Ⅱ（Ang Ⅱ） in primary cultured neonatal rat cardiac myocytes. Methods： The effect of STS ...Objective： To investigate the effects of sodium tanshinone Ⅱ A sulfonate （STS） on the hypertrophy induced by angiotensin Ⅱ（Ang Ⅱ） in primary cultured neonatal rat cardiac myocytes. Methods： The effect of STS on cytotoxicity was evaluated using the 3-（4,5-dimethylthiazol-2-yl）-3,5- phenytetrazoliumromide （MTT） assay. As indexes for cardiocyte hypertrophy, cell size was determined by phase contrast microscopy and protein synthesis rate was measured by 3H-leucine incorporation. The proto-oncogene c-fos mRNA expression of cardiocytes was assessed using reverse transcription polymerase chain reaction （RT-PCR）. Results： STS could inhibit cardiocyte hypertrophy, increase the protein synthesis rate and enhance proto-oncogene c-fos mRNA expression in cardiocytes induced by Ang Ⅱ（P〈0.01）, with an effect similar to that of Valsartan, the Ang Ⅱ receptor antagonist. Conclusion： STS can prevent the hypertrophy of cardiac myocytes induced by Ang Ⅱ, which may be related to its inhibition of the expression of proto-oncogene c-fos mRNA.展开更多
目的观察尾加压素Ⅱ(Urotensin Ⅱ,U Ⅱ)对心肌细胞肥大的效应。方法以体外培养的SD乳鼠心肌细胞为实验模型,分为正常对照组,单纯UⅡ作用组,环胞素A(CsA)阻断组。用real-time PCR方法分析β-MHC、CaN(钙调神经磷酸酶) mRNA表达的变化,...目的观察尾加压素Ⅱ(Urotensin Ⅱ,U Ⅱ)对心肌细胞肥大的效应。方法以体外培养的SD乳鼠心肌细胞为实验模型,分为正常对照组,单纯UⅡ作用组,环胞素A(CsA)阻断组。用real-time PCR方法分析β-MHC、CaN(钙调神经磷酸酶) mRNA表达的变化,用免疫印迹法(Western blot)研究心肌肥大过程中β-MHC、CaN蛋白表达的变化,探讨UⅡ对心肌细胞肥大的影响。结果①随着UⅡ浓度的增加,心肌细胞β-MHC、CaN mRNA和蛋白表达明显增加,其中10-8、10-7mol/L U Ⅱ组与对照组相比较差异显著(P<0.05);②用10-8mol/L U Ⅱ处理心肌细胞12、24、48 h,随着时间增加,心肌细胞β-MHC、CaN mRNA和蛋白表达呈递增趋势,其中处理24h组与正常对照组有显著差异(P<0.05);③预先用环胞素A5μmol/L(cyclosporin A CsA)处理正常心肌细胞24 h,然后用10-8mol/L U Ⅱ作用24 h,心肌细胞β-MHC、CaN mRNA和蛋白表达与正常心肌细胞经10-8mol/L U Ⅱ单纯作用24 h差异有显著意义(P<0.05)。结论 U Ⅱ能够诱导心肌细胞的肥大,环胞素A(CsA)能阻断此效应,CaN参与了UⅡ诱导的心肌肥大过程。展开更多
文摘Objective To study the effects of simvastatin on the hypertrophy of cultured rat cardiac myocytes induced by serum and the role ofphosphatase and tensin homolog deleted on chromosome ten （PTEN） in the signal pathway. Methods Cultured neonatal Sprague- Dawley （SD） rat cardiac myocytes were treated with 15% fetal bovine serum, or without serum, or different consentrations of simvastatin. Image analysis system was used to measure the cardiac myocytes surface area. Protein synthesis of myocytes was measured via [3H]-leucine incorporation method. The expression level of atrial natriuretic peptide （ANP） mRNA in myocytes was determined with reverse transcription polymerase chain reaction （RT-PCR）. The mRNA and protein expression levels of PTEN in cardiac myocytes were investigated with RT-PCR and Western blot respectively. Results At 24 hours, cardiac myocytes surface area was significantly higher in 15% serum group （1611.16± 160.75 lam2） than in serum-free group （538.04±118.60 ±tm2, P〈0.01）. Simvastatin decreased the cell surface area in a concentration dependent manner. The cell surface area in 10-5 and 10-6 mol/L simvastatin groups were 799.84＋ 167.70 ±tm2 and 1076.88± 199.28 um2 respectively, which were both significantly lower than that in 15% fetal bovine serum group （P〈0.01）. Incorporation rate of [3H]-leucine was significantly higher in 15% fetal bovine serum group （2360± 106cpm/well） than that in serum-free group （1305±92 cpm/well, P〈0.01）. Incorporation rate of [3H]-leucine in 10.5 and 10.6 mol/L simvastatin groups were 1707±101 clam/well and 1962±125 cpm/well respectively, which were both lower than that in serum group （P〈0.01）. With the increase of simvastatin concentration, the expression level ofANP mRNA in cardiac myocytes was decreased gradually, which were 0.29±0.03 and 0.40-±0.03 respectively in 10.5 and 10-6 mol/L simvastatin groups, and significantly lower than that in serum group（0.60-±.03, P〈0.01）. Simvastatin increased the expressions of PTEN mRNA and protein in cardiac myocytes in a concentration dependent manner. PTEN mRNA expression level in 10-7, 10-6and 105mol/L simvastatin groups were 0.38±0.03, 0.83±0.04 and 0.85±0.05, respectively, which were all higher than that in 15% fetal bovine serum group （0.29±0.04, P〈0.05）. Similarly, PTEN protein level in 10-7, 10-6 and 10.5 mol/L simvastatin groups （39.25±3.41, 46.35±1.78 and 47.22±2.39 respectively） were also significantly higher than that in 15% fetal bovine serum group （32.21±4.06, P〈0.05）. Conclusion Simvastatin can inhibit the hypertrophy of cultured rat cardiac myoeytes induced by serum, and the increase of expression level of PTEN might be involved in the mechanism （J Geriatr Cardio12010; 7：47-51）.
文摘Objective:Cardiac hypertrophy is an adaptive reaction of the heart against cardiac overloading,but continuous cardiac hypertrophy can lead to cardiac remodeling and heart failure.Cardiac hypertrophy is mostly considered reversible,and recent studies have indicated that decorin not only prevents cardiac fibrosis associated with hypertension,but also achieves therapeutic effects by blocking fibrosis-related signaling pathways.However,the mechanism of action of decorin remains unknown and unconfirmed.Methods:We determined the degree of myocardial hypertrophy by measuring the ratios of the heart weight/body weight and left ventricular weight/body weight,histological analysis and immunohistochemistry.Western blotting was performed to detect the expression levels of CaMKⅡ,p-CaMKⅡ and MEF-2 in the heart.Results:Our results confirmed that decorin can regulate the CaMKⅡ/MEF-2 signaling pathway,with inhibition thereof being similar to that of decorin in reducing cardiac hypertrophy.Conclusion:Taken together,the results of the present study showed that decorin induced cardiac hypertrophy by regulating the CaMKⅡ/MEF-2 signaling pathway in vivo,revealing a new therapeutic approach for the prevention of cardiac hypertrophy.
基金the National Natural Science Foundation of China(No.30500657)
文摘Objective： To investigate the effects of sodium tanshinone Ⅱ A sulfonate （STS） on the hypertrophy induced by angiotensin Ⅱ（Ang Ⅱ） in primary cultured neonatal rat cardiac myocytes. Methods： The effect of STS on cytotoxicity was evaluated using the 3-（4,5-dimethylthiazol-2-yl）-3,5- phenytetrazoliumromide （MTT） assay. As indexes for cardiocyte hypertrophy, cell size was determined by phase contrast microscopy and protein synthesis rate was measured by 3H-leucine incorporation. The proto-oncogene c-fos mRNA expression of cardiocytes was assessed using reverse transcription polymerase chain reaction （RT-PCR）. Results： STS could inhibit cardiocyte hypertrophy, increase the protein synthesis rate and enhance proto-oncogene c-fos mRNA expression in cardiocytes induced by Ang Ⅱ（P〈0.01）, with an effect similar to that of Valsartan, the Ang Ⅱ receptor antagonist. Conclusion： STS can prevent the hypertrophy of cardiac myocytes induced by Ang Ⅱ, which may be related to its inhibition of the expression of proto-oncogene c-fos mRNA.
文摘目的观察尾加压素Ⅱ(Urotensin Ⅱ,U Ⅱ)对心肌细胞肥大的效应。方法以体外培养的SD乳鼠心肌细胞为实验模型,分为正常对照组,单纯UⅡ作用组,环胞素A(CsA)阻断组。用real-time PCR方法分析β-MHC、CaN(钙调神经磷酸酶) mRNA表达的变化,用免疫印迹法(Western blot)研究心肌肥大过程中β-MHC、CaN蛋白表达的变化,探讨UⅡ对心肌细胞肥大的影响。结果①随着UⅡ浓度的增加,心肌细胞β-MHC、CaN mRNA和蛋白表达明显增加,其中10-8、10-7mol/L U Ⅱ组与对照组相比较差异显著(P<0.05);②用10-8mol/L U Ⅱ处理心肌细胞12、24、48 h,随着时间增加,心肌细胞β-MHC、CaN mRNA和蛋白表达呈递增趋势,其中处理24h组与正常对照组有显著差异(P<0.05);③预先用环胞素A5μmol/L(cyclosporin A CsA)处理正常心肌细胞24 h,然后用10-8mol/L U Ⅱ作用24 h,心肌细胞β-MHC、CaN mRNA和蛋白表达与正常心肌细胞经10-8mol/L U Ⅱ单纯作用24 h差异有显著意义(P<0.05)。结论 U Ⅱ能够诱导心肌细胞的肥大,环胞素A(CsA)能阻断此效应,CaN参与了UⅡ诱导的心肌肥大过程。
