Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China (mainland).
Department of Anesthesiology, Jinshan Hospital, Fudan University, Shanghai, China (mainland).
Med Sci Monit. 2021 May 19;27:e930478. doi: 10.12659/MSM.930478.
BACKGROUND Propofol improves rodent pulmonary injury after intestinal ischemia-reperfusion (IIR). However, its effect and underlying mechanisms in large animals remain unclear. Here, we examined whether pretreatment with propofol could relieve lung injury during IIR in pigs, then investigated the underlying mechanism. MATERIAL AND METHODS A porcine model of IIR-induced lung injury was built by clamping the super mesenteric artery for 2 h and loosening the clamp for 4 h. Randomized grouping was used, and pigs were assigned to a sham-operated group, an IIR with saline pretreatment group, and an IIR with propofol pretreatment group. Pulmonary histopathologic changes, permeability, and oxygenation were assessed to evaluate the effect of propofol. We assessed levels of methane dicarboxylic aldehyde (MDA), superoxide dismutase (SOD), myeloperoxidase (MPO), high-mobility group box 1 protein (HMGB1), Toll-like receptor 4 (TLR4), and double-stranded RNA activated protein kinase R (PKR) to investigate the underlying mechanism. RESULTS IIR caused severe lung damage, including morphological changes, high permeability, airway resistance, low static compliance, hypoxemia, and acidemia. Pulmonary and plasma MDA content and MPO activity increased, whereas SOD activity decreased. The HMGB1/TLR4/PKR signaling pathway was activated following IIR. Pretreatment with propofol markedly attenuated lung injury (such as reducing the lung edema and permeability), increased MDA content and MPO activity, and restored SOD activity induced by IIR, accompanied by inhibiting the effect of the HMGB1/TLR4/PKR signaling pathway. CONCLUSIONS IIR caused acute lung injury in pigs. Pretreatment with propofol alleviated the lung injury, which was related to its suppression of the HMGB1/TLR4/PKR signaling pathway.
异丙酚可改善肠缺血再灌注（IIR）后的啮齿动物肺损伤。然而，其在大动物中的作用和潜在机制尚不清楚。在此，我们研究了异丙酚预处理是否可以减轻猪的 IIR 期间的肺损伤，然后研究了潜在的机制。
通过夹闭肠系膜上动脉 2 小时并松开夹闭 4 小时，建立猪的 IIR 诱导的肺损伤模型。采用随机分组，将猪分为假手术组、盐水预处理 IIR 组和异丙酚预处理 IIR 组。评估肺组织病理学变化、通透性和氧合情况，以评估异丙酚的作用。评估甲烷二羧酸醛（MDA）、超氧化物歧化酶（SOD）、髓过氧化物酶（MPO）、高迁移率族蛋白 B1（HMGB1）、Toll 样受体 4（TLR4）和双链 RNA 激活蛋白激酶 R（PKR）的水平，以探讨潜在机制。
IIR 导致严重的肺损伤，包括形态学改变、高通透性、气道阻力增加、静态顺应性降低、低氧血症和酸中毒。肺组织和血浆 MDA 含量和 MPO 活性增加，而 SOD 活性降低。HMGB1/TLR4/PKR 信号通路在 IIR 后被激活。异丙酚预处理可显著减轻肺损伤（如减少肺水肿和通透性），增加 MDA 含量和 MPO 活性，恢复 IIR 诱导的 SOD 活性，并抑制 HMGB1/TLR4/PKR 信号通路的作用。
IIR 导致猪急性肺损伤。异丙酚预处理减轻了肺损伤，这与其抑制 HMGB1/TLR4/PKR 信号通路有关。
