Department of Pathophysiology, Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, China.
World J Surg. 2010 Jul;34(7):1676-83. doi: 10.1007/s00268-010-0493-5.
The histone deacetylase (HDAC) inhibitors have emerged as the useful reagents that epigenetically modulate the expression of various genes. In the present study, the effects of HDAC inhibitors on the expression of inflammation-related genes and lung injury during sepsis were investigated.
Mice were pretreated with two structurally unrelated HDAC inhibitors, Trichostatin A (TSA) and sodium butyrate (SB). Thirty minutes later, mice underwent cecal ligation and puncture (CLP)-induced sepsis. Lung injury and the expression of inflammation-related molecules were determined. In addition, survival was assessed post-CLP.
Our results indicated that administration of TSA or SB alleviated sepsis-induced lung injury. This was accompanied by reduced neutrophil infiltration, decreased intercellular adhesion molecule-1 (ICAM-1) and E-selectin expression in lung tissue, and lower interleukin-6 (IL-6) level in plasma. In addition, treatment with HDAC inhibitors significantly prolonged the survival time of CLP mice.
These data indicated that the HDAC inhibitors, based on modulating the key enzymes linked to acetylation modification, effectively attenuate intrapulmonary inflammatory response, thus significantly alleviating lung injury during sepsis.
组蛋白去乙酰化酶（HDAC）抑制剂已成为具有潜力的试剂，可以通过表观遗传方式调节各种基因的表达。本研究旨在探讨 HDAC 抑制剂对脓毒症相关炎症基因表达和肺损伤的影响。
采用两种结构不同的 HDAC 抑制剂，曲古抑菌素 A（TSA）和丁酸钠（SB）预处理小鼠。30 分钟后，进行盲肠结扎穿孔（CLP）诱导的脓毒症。检测肺损伤和炎症相关分子的表达情况，并评估 CLP 后的生存率。
结果表明，给予 TSA 或 SB 可减轻脓毒症引起的肺损伤。这与肺组织中中性粒细胞浸润减少、细胞间黏附分子-1（ICAM-1）和 E-选择素表达降低以及血浆中白细胞介素-6（IL-6）水平降低有关。此外，HDAC 抑制剂治疗还显著延长了 CLP 小鼠的生存时间。
这些数据表明，基于调节与乙酰化修饰相关的关键酶的 HDAC 抑制剂，可有效减轻肺内炎症反应，从而显著减轻脓毒症期间的肺损伤。
