中文摘要：

目的 利用体外培养的大鼠乳鼠心肌细胞,研究曲古霉素（TSA）对血管紧张素Ⅱ（AngⅡ）诱导的心肌细胞肥大的影响,并探讨相关机制.方法 分离乳鼠心肌细胞进行原代培养,应用血管紧张素Ⅱ制备心肌细胞肥大模型.分别给予不同浓度的TSA预处理心肌细胞,观察TSA对心肌细胞面积、3H亮氨酸掺入率、心房利钠肽（ANP）、脑利钠肽（BNP）的mRNA表达水平的影响.同时通过检测乙酰化组蛋白3的蛋白表达水平,观察AngⅡ和TSA对组蛋白脱乙酰基酶（HDAC）活性的影响.应用Western blot检测AngⅡ和TSA处理后磷酸化的c-Jun氨基末端激酶（JNK）表达水平的变化.结果 10-6 mmol/L AngⅡ作用48 h后,心肌细胞面积增加至对照组的（1.63±0.46）倍（P＜0.01）,而10-7mmol/L和3＆#215;10-7 mmoL/L TSA预处理可以剂量依赖性的抑制AngⅡ引起的心肌细胞面积增大.TSA干预也阻断了AngⅡ引起的蛋白合成速率增加以及ANP和BNP的蛋白表达水平的增加（均为P＜0.05）.AngⅡ刺激心肌细胞使乙酰化组蛋白3的蛋白表达水平降低,TSA可逆转这一效应.同时TSA抑制了AngⅡ介导的磷酸化JNK表达水平的升高.结论 TSA可显著抑制AngⅡ诱导的心肌细胞肥大和HDAC活性增加,可能通过抑制JNK的激活而发挥抑制心室肥厚的作用.

英文摘要：

Objective To investigate the effects of trichostatin （TSA） on neonatal rat cardiomyocyte hypertrophy induced by angiotensinⅡ （Ang Ⅱ ） infusion. Methods Primary cultured neonatal rat cardiomyocytes were treated with angiotensin 1I with or in the absence of TSA pretreatment. Cardiomyoeytes cross area, [ 3 H ] Leueine incorporation rate, as well as mRNA expression level of ANP and BNP, were measured. The protein expression level of acetylated bistone H3 and phosphorylated JNK was also examined. Results The cardiomyocyte cross area enlarged to （ 1.63 ±0.46 ） times to the original, which was blunted by pretreatment of TSA at the dosage of 10 ^-7 mmol/L and 3 x 10 ^7 mmol/L. Increased protein synthesis rates and upregulation of mRNA expression of ANP as well as BNP by Ang II stimulation, were also blocked by TSA treatment. The protein expressions of acetylated histone H3, as well as phosphorylated JNK were upregulated by AngⅡ induction, which were also inhibited by TSA. Conclusions TSA pretreatment blunts cardiomyocyte hypertrophy induced by Ang Ⅱ infusion, which is possibly due to theinhibition of total histone deacetylase （HDAC） activity and JNK activation.