Department of Anesthesiology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou 215004, People's Republic of China.
J Anesth. 2013 Apr;27(2):251-60. doi: 10.1007/s00540-012-1494-3. Epub 2012 Nov 10.
Delayed volatile anesthetic preconditioning (APC) can protect against myocardial ischemia/reperfusion (I/R) injury; the delayed phase is called the second window of protection (SWOP), but the underlying mechanism is unclear. Nuclear factor-κB (NF-κB) is involved in the myocardial protection conferred by APC in the acute phase; autophagy has been reported to confer apoptosis inhibition and infarction reduction. We hypothesized that APC initiates delayed cardioprotection against I/R injury via the activation of NF-kB and upregulation of autophagy, thus attenuating the inflammatory response and apoptosis
After a rat I/R model was set up, left ventricular samples were obtained before I/R to assess NF-κB-DNA binding activity and microtubule-associated protein 1 light chain 3 (LC3) and cathepsin B protein expression, and to examine autophagosomes with a transmission electron microscope. Infarct size and the expressions of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and caspase-3 were measured at the end of 2-h reperfusion.
The infarct size was significantly reduced in the SWOP group (30 ± 3 %) when compared with that in the I/R group (47 ± 7 %, P < 0.05), and this finding was associated with increased NF-κB-DNA binding activity and autophagosomes. In addition, the expressions of LC3-II and cathepsin B were also up-regulated, and the expressions of TNF-α, IL-1β, and caspase-3 were attenuated in the SWOP group when compared with the findings in the I/R group. However, this protection was abolished by the administration of parthenolide (PTN) before sevoflurane inhalation, which resulted in an infarct size that was significantly increased (47 ± 5 %, P < 0.05 PTN + SWOP vs. SWOP group).
Delayed APC protected the rat heart from I/R injury. The underlying mechanisms may include NF-κB activation, upregulation of autophagy, and the attenuation of TNF-α, IL-1β, and caspase-3 expressions.
延迟挥发性麻醉预处理（APC）可预防心肌缺血/再灌注（I/R）损伤；延迟阶段称为第二保护窗口（SWOP），但其潜在机制尚不清楚。核因子-κB（NF-κB）参与 APC 在急性期产生的心肌保护作用；自噬已被报道可抑制细胞凋亡并减少梗死。我们假设 APC 通过激活 NF-kB 和上调自噬来启动对 I/R 损伤的延迟心脏保护作用，从而减轻炎症反应和细胞凋亡。
建立大鼠 I/R 模型后，在 I/R 前获取左心室样本，评估 NF-κB-DNA 结合活性以及微管相关蛋白 1 轻链 3（LC3）和组织蛋白酶 B 蛋白的表达，并使用透射电子显微镜检查自噬体。在 2 小时再灌注结束时测量梗死面积以及肿瘤坏死因子-α（TNF-α）、白细胞介素 1β（IL-1β）和半胱氨酸天冬氨酸蛋白酶 3 的表达。
SWOP 组（30±3%）的梗死面积明显小于 I/R 组（47±7%，P<0.05），并且这种情况与 NF-κB-DNA 结合活性和自噬体的增加有关。此外，LC3-II 和组织蛋白酶 B 的表达也上调，SWOP 组的 TNF-α、IL-1β和半胱氨酸天冬氨酸蛋白酶 3 的表达也减弱。然而，在给予七氟醚吸入前给予小白菊内酯（PTN）后，这种保护作用被消除，导致梗死面积明显增加（47±5%，P<0.05，PTN+SWOP 与 SWOP 组相比）。
延迟 APC 可保护大鼠心脏免受 I/R 损伤。其潜在机制可能包括 NF-κB 激活、自噬上调以及 TNF-α、IL-1β 和半胱氨酸天冬氨酸蛋白酶 3 表达的减弱。
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