Department of Anesthesiology, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, Fujian Province, China.
Shock. 2020 Oct;54(4):474-481. doi: 10.1097/SHK.0000000000001505.
This study aimed to assess the severity of acute lung injury after mild or severe hemorrhagic shock and resuscitation, and to examine the therapeutic effects of suberoylanilide hydroxamic acid (SAHA) on lung injury.
Mild and severe hemorrhagic shock were induced by total blood volume loss of 20% or 40%, respectively, which was maintained for 60 min. Then, resuscitation was performed by autologous blood and SAHA or a vehicle solution accordingly. Mean arterial pressure, heart rate, and arterial blood gas were measured during the experiment. Histological assays, wet/dry weight ratio, inflammatory cytokines, and the extent of histone acetylation were evaluated at 3 h post-resuscitation.
There were no significant differences of the most indicators measured between the mild hemorrhagic shock and Sham groups. Although in severe hemorrhagic shock group, mean arterial pressure was markedly reduced, lactic acid was significantly increased after hemorrhage. Moreover, the lung injury score was increased, the wet/dry weight ratio was elevated, inflammatory factor expression levels were upregulated, the expression of phosphorylated NF-κB/p65 was enhanced, and the extent of histone acetylation was decreased at 3 h post-resuscitation. Remarkably, adjuvant treatment with SAHA decreased the lactic acid, the pathological injury score, the wet/dry weight ratio, the content of inflammatory factor, as well as the level of activated NF-κB/p65, but promoted the expression of acetylated H4.
Total blood volume loss of 40% results in acute lung injury, whereas loss of 20% does not. Treatment with SAHA alleviates lung injury induced by severe hemorrhagic shock and resuscitation and the underlying mechanism involves a reversal of decreased histone acetylation and inhibition of the NF-κB pathway.
本研究旨在评估轻度或重度失血性休克及复苏后急性肺损伤的严重程度，并探讨琥珀酸酰苯胺水解酶（SAHA）对肺损伤的治疗作用。
通过全血容量损失 20%或 40%分别诱发轻度和重度失血性休克，各维持 60 分钟。然后，通过自体血和 SAHA 或相应的载体溶液进行复苏。实验过程中测量平均动脉压、心率和动脉血气。在复苏后 3 小时评估组织学检测、湿/干重比、炎性细胞因子和组蛋白乙酰化程度。
轻度失血性休克和假手术组之间的大多数指标测量值没有显著差异。尽管在重度失血性休克组中，平均动脉压明显降低，出血后乳酸明显增加。此外，肺损伤评分增加，湿/干重比升高，炎性因子表达水平上调，磷酸化 NF-κB/p65 的表达增强，组蛋白乙酰化程度降低。值得注意的是，SAHA 的辅助治疗降低了乳酸、病理损伤评分、湿/干重比、炎性因子含量以及活化的 NF-κB/p65 水平，但促进了乙酰化 H4 的表达。
全血容量损失 40%会导致急性肺损伤，而损失 20%则不会。SAHA 治疗可减轻严重失血性休克及复苏引起的肺损伤，其潜在机制涉及逆转组蛋白乙酰化降低和抑制 NF-κB 途径。
