Cai Ying, Zhang Hong, Cui Lun-Meng, Chen Qian, Xie Feng-Jie
Department of Critical Care Medicine, Hongqi Hospital affiliated to Mudanjiang Medical University, Mudanjiang City, Heilongjiang Province, China.
PLoS One. 2025 May 8;20(5):e0322653. doi: 10.1371/journal.pone.0322653. eCollection 2025.
This study aimed to investigate the effects of lidocaine on sepsis-induced acute lung injury and its underlying mechanisms.
Thirty C57BL/6 mice were divided into three groups: SHAM, CLP, and LD. The sepsis-induced acute lung injury model was established using cecal ligation and puncture (CLP) surgery, while SHAM mice underwent a sham operation without ligation or puncture. Mice in the LD group were administered lidocaine (10 mg/kg) intravenously through the tail vein. The SHAM and CLP groups were treated with an equal volume of 0.9% sterile saline solution. All mice were sacrificed 24 hours after surgery, and lung tissue and blood samples were collected for subsequent analysis. The wet/dry weight ratio (W/D ratio) was measured to evaluate lung edema. Lung injury and apoptosis were assessed using HE staining and TUNEL assay. The concentrations of inflammatory cytokines IL-6, TNF-α, and HMGB1 were measured by ELISA. The expression of JAK2, STAT3, p-STAT3, Bcl-2, HMGB1, and Bax was analyzed by western blot.
The W/D ratio in the CLP group was significantly higher than the SHAM group, indicating increased lung edema. Pathological examination revealed obvious lung injury, and apoptosis was evident in the CLP group. The expression of HMGB1, IL-6, and TNF-α in lung tissue increased by 24 hours after CLP surgery. Additionally, the levels of JAK2, STAT3, p-STAT3, HMGB1, and Bax were significantly increased, while Bcl-2 expression was reduced. However, lidocaine administration reversed these changes.
Intravenous lidocaine effectively alleviated acute lung injury in septic mice. The anti-inflammatory effects of lidocaine may be attributed to its suppression of the JAK2/STAT3 signaling pathway and its anti-apoptotic effects.
本研究旨在探讨利多卡因对脓毒症诱导的急性肺损伤的影响及其潜在机制。
将30只C57BL/6小鼠分为三组：假手术组（SHAM）、盲肠结扎穿孔组（CLP）和利多卡因组（LD）。采用盲肠结扎穿孔（CLP）手术建立脓毒症诱导的急性肺损伤模型，而假手术组小鼠进行未结扎或穿孔的假手术。利多卡因组小鼠通过尾静脉静脉注射利多卡因（10 mg/kg）。假手术组和盲肠结扎穿孔组用等量的0.9%无菌盐溶液治疗。所有小鼠在手术后24小时处死，收集肺组织和血液样本用于后续分析。测量湿/干重比（W/D比）以评估肺水肿。使用苏木精-伊红（HE）染色和末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）法评估肺损伤和细胞凋亡。通过酶联免疫吸附测定（ELISA）测量炎性细胞因子白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和高迁移率族蛋白B1（HMGB1）的浓度。通过蛋白质免疫印迹法分析Janus激酶2（JAK2）、信号转导和转录激活因子3（STAT3）、磷酸化信号转导和转录激活因子3（p-STAT3）、B细胞淋巴瘤-2（Bcl-2）、HMGB1和Bax的表达。
盲肠结扎穿孔组的W/D比显著高于假手术组，表明肺水肿增加。病理检查显示明显的肺损伤，且盲肠结扎穿孔组细胞凋亡明显。盲肠结扎穿孔手术后24小时，肺组织中HMGB1、IL-6和TNF-α的表达增加。此外，JAK2、STAT3、p-STAT3、HMGB1和Bax的水平显著升高，而Bcl-2表达降低。然而，给予利多卡因可逆转这些变化。
静脉注射利多卡因可有效减轻脓毒症小鼠的急性肺损伤。利多卡因的抗炎作用可能归因于其对JAK2/STAT3信号通路的抑制及其抗细胞凋亡作用。
