丙戊酸对AngⅡ诱导的心肌细胞肥大与HDAC2表达的抑制作用

Valproic acid inhibits cardiomyocyte hypertrophy and HDAC2 expressions induced by angiotensin II

目的:观察组蛋白脱乙酰基酶抑制剂—丙戊酸(valproic acid,VPA)抑制心肌细胞肥大和组蛋白脱乙酰基酶2(histone deacetylase 2,HDAC2)的表达。方法:常规方法培养原代心肌细胞,分为5组:对照组、肥大组、低浓度VPA组(5×10-6mol/L)、中浓度VPA组(10-5mol/L)和高浓度VPA组(2×10-5mol/L)。给予血管紧张素Ⅱ(AngⅡ)刺激心肌细胞造成肥大后,给予不同浓度的VPA进行干预。AngⅡ作用24 h后,于相差显微镜下观察心肌细胞面积的变化。用RT-PCR检测HDAC2 mRNA的表达;免疫组化染色法检测HDAC2蛋白的表达。结果:经AngⅡ刺激后,在相差显微镜下可见心肌细胞面积变大,HDAC2 mRNA的水平增高,HDAC2蛋白表达亦增加。给予不同浓度的VPA后,上述指标随着VPA浓度的增加而逐渐下降(P<0.05)。结论:AngⅡ致心肌细胞肥大的过程中伴有HDAC2表达增加,给予HDAC抑制制后,可使心肌细胞面积减少,HDAC2表达减少,提示VPA可抑制心肌细胞的肥大,HDAC2有可能参与心肌细胞肥大的机制。

AIM： To observe the expression of histone deacetylase 2 （HDAC2） in hypertrophic cardiomyeytes induced by angiotensin Ⅱ （Ang Ⅱ） and to study the inhibitory role of valproic acid （VPA）. METHODS： Cultured cardiomyocytes were treated with AngⅡ to induce hypertrophy, along with VPA of different concentrations. They were divided randomly into control group, hypertrophic group, and low （5×10^-6 mol/L）, medium （10^-5 tool/L） and high concentration （2 ×10^-5 mol/L） group. Morphological changes of eardiomyocytes were observed under the contrast phase microscope, mRNA levels of HDAC2 were examined by reverse transcriptase polymerase chain reaction （RT-PCR）. Protein expressions of HDAC2 were examined by immunohistochemistry. RESULTS： Stimulated by Ang Ⅱ, cardiomyoeytes were enlarged under the contrast phase microscope. After stimulation by AngⅡ, the mRNA level of HDAC2 and the protein expression of HDAC2 increased in the hypertrophic cardiocytes. Along with VPA, these data decreased accordingly as the VPA concentrations increased. CONCLUSION： Expression of HDAC2 increased in hypertrophic cardiomyocytes stimulated by Ang Ⅱ. HDAC2 may play a role in cardiocyte hypertrophy. VPA may inhibit cardiomyocyte hypertrophy and HDAC2 expressions.