中文摘要：

目的：观察组蛋白脱乙酰化酶抑制剂曲古抑菌素A（TSA）对心肌梗死后心衰（HF）大鼠心脏肿瘤坏死因子（TNF-α）、白细胞介素-1β（IL-1β）和诱导型一氧化氮合酶（iNOS）及心功能的影响。方法：采用冠状动脉左前降支结扎术致心肌梗死制备大鼠HF模型和假手术模型（sham）,给予TSA或vehicle处理。给药4周后,测定血流动力学参数,应用免疫组织化学和ELISA检测左室心肌TNF-α、IL-1β和iNOS的水平,并测定右室/体重（RV/BW）、肺重/体重（LW/BW）。结果：与HF＋vehide组相比,给予TSA后可使HF大鼠心肌组织内增高的TNF-α、IL-1β和iNOS含量明显降低（P〈0.05）,左室舒张末压（LVEDP）和LW/BW降低（P〈0.05）;降低的左室内压最大上升速率（＋dp/dtmax）和左室内压最大下降速率（-dp/dtmax）明显升高（P〈0.05）。结论：组蛋白脱乙酰化酶抑制剂TSA抑制心肌梗死后HF大鼠心肌组织TNF-α、IL-1β及iNOS的产生,并且可能通过该抑制作用改善HF大鼠的心功能,减轻肺淤血。

英文摘要：

AIM： To observe the effects of histone deacetylase inhibitor trichostatin A（TSA） on the expression of tumor necrosis factor α（TNF-α）,interleukin 1β（IL-1β） and inducible nitric oxide synthase（iNOS） in hearts and cardiac function in rats with heart failure（HF）. METHODS： Sprague-Dawley rats were subjected to coronary artery ligation to induce HF,or sham surgery（sham）.Subsequently,the animals were treated with TSA or vehicle（VEH） for 4 weeks.After 4 weeks,the haemodynamic,the anatomical parameters and the levels of TNF-α,IL-1β and iNOS in hearts were measured. RESULTS： After treated with TSA,the levels of TNF-α,IL-1β and iNOS in hearts and left ventricular end-diastolic pressure（LVEDP）,lung weight/body weight（LW/BW） were reduced（P〈0.05）,while ＋dp/dtmax and-dp/dtmax were increased in heart failure rats（P〈0.05）. CONCLUSION： These findings indicate that histone deacetylase inhibitor TSA may improve cardiac function and attenuate pulmonary congestion in rats with HF via inhibiting TNF-α,IL-1β and iNOS production in hearts.