曲古抑菌素A对心衰大鼠心脏促炎细胞因子及心功能的影响

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 1 β( IL - 1 β ) 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 ).Suhsequently, 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 - 1 β and iNOS production in hearts.%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.