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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。
Objective: To investigate the effect 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) and cardiac function. Methods: HF model and sham operation model were established by coronary artery ligation of left anterior descending artery in rats. TSA or vehicle treatment was used. After 4 weeks of administration, the hemodynamic parameters were measured. The levels of TNF-α, IL-1β and iNOS in left ventricular myocardium were detected by immunohistochemistry and ELISA, and the RV / BW, Weight (LW / BW). Results: Compared with HF + vehide group, TSA increased the levels of TNF-α, IL-1β and iNOS in HF rats significantly (P <0.05), left ventricular end-diastolic pressure LW / BW decreased (P <0.05); decreased left ventricular pressure maximum rate of increase (+ dp / dtmax) and left ventricular pressure maximum rate of decline (-dp / dtmax) increased significantly (P <0.05). Conclusion: The histone deacetylase inhibitor TSA can inhibit the production of TNF-α, IL-1β and iNOS in myocardial tissue of HF rats after myocardial infarction, and may improve heart function and lung congestion of HF rats by this inhibition.