Department of Anesthesiology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China; Department of Anesthesiology, Mindong Hospital Affiliated to Fujian Medical University, Fuan 355000, Fujian, China.
Department of Anesthesiology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China; Department of Anesthesiology, Heze Municipal Hospital, Heze 274000, China.
Int Immunopharmacol. 2024 Sep 30;139:112725. doi: 10.1016/j.intimp.2024.112725. Epub 2024 Jul 25.
To investigate esketamine's impact on inflammation and oxidative stress in ventilated chronic obstructive pulmonary disease (COPD) rats, examining its regulatory mechanisms.
Rats were divided into four groups: control group (Con), COPD model group (M), COPD model with saline treatment group (M+S), and COPD model with esketamine treatment group (M+K), with 12 rats in each group. After two months, all rats underwent anesthesia and mechanical ventilation. Group M+K received 5 mg/kg esketamine intravenously, while Group M+S received the same volume of saline. Lung tissues were collected for analysis two hours later, including airway peak pressure, wet-to-dry(W/D) ratio, lung permeability index(LPI), hematoxylin and eosin(H&E) staining, and transmission electron microscopy(TEM). Tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-8(IL-8), and interleukin-10(IL-10) levels were determined by enzyme-linked immunosorbent assay(ELISA); phosphorylated Nuclear Factor Kappa B(p-NF-κB), mitogen-activated protein kinase 14(p38), phosphorylated p38 (p-p38), c-Jun N-terminal kinase(JNK), and phosphorylated JNK (p-JNK) expressions by Western blotting and immunohistochemistry; and malondialdehyde(MDA), myeloperoxidase(MPO), and superoxide dismutase(SOD) levels were also measured by corresponding biochemical assays.
Lung specimens from groups M, M+S, and M+K manifested hallmark histopathological features of COPD. Compared with group Con, group M displayed increased peak airway pressure, W/D ratio, and LPI. In group M+K, compared with group M, esketamine significantly reduced the W/D ratio, LPI, and concentrations of pro-inflammatory cytokines TNF-α, IL-6, and IL-8 while concurrently elevating IL-10 levels. Furthermore, the treatment attenuated the activation of the NF-κB and MAPK pathways, indicated by decreased levels of p-NF-κB, p-p38, and p-JNK.Additionally, compared to group M, group M+K showed decreased MDA and MPO levels and increased SOD levels in lung tissue.
Esketamine attenuates mechanical ventilation-induced lung injury in COPD rat models by inhibiting the MAPK/NF-κB signaling pathway and reducing oxidative stress.
研究氯胺酮对机械通气慢性阻塞性肺疾病（COPD）大鼠炎症和氧化应激的影响，探讨其调控机制。
将大鼠分为四组：对照组（Con）、COPD 模型组（M）、COPD 模型盐水治疗组（M+S）和 COPD 模型氯胺酮治疗组（M+K），每组 12 只大鼠。两个月后，所有大鼠均行麻醉和机械通气。M+K 组给予 5mg/kg 氯胺酮静脉注射，M+S 组给予相同体积的生理盐水。2 小时后取肺组织，检测气道峰压、湿干重比（W/D）、肺通透性指数（LPI）、苏木精-伊红（H&E）染色和透射电镜，酶联免疫吸附试验（ELISA）检测肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和白细胞介素-10（IL-10）水平，Western blot 和免疫组化检测磷酸化核因子-κB（p-NF-κB）、丝裂原活化蛋白激酶 14（p38）、磷酸化 p38（p-p38）、c-Jun N-末端激酶（JNK）和磷酸化 JNK（p-JNK）表达，相应生化检测试剂盒检测丙二醛（MDA）、髓过氧化物酶（MPO）和超氧化物歧化酶（SOD）水平。
M、M+S 和 M+K 组肺组织均表现出 COPD 的标志性组织病理学特征。与 Con 组比较，M 组气道峰压、W/D 比和 LPI 均升高；与 M 组比较，M+K 组 W/D 比、LPI 和促炎细胞因子 TNF-α、IL-6、IL-8 浓度降低，IL-10 水平升高；MAPK/NF-κB 信号通路活化减轻，p-NF-κB、p-p38 和 p-JNK 表达降低。与 M 组比较，M+K 组肺组织 MDA 和 MPO 水平降低，SOD 水平升高。
氯胺酮通过抑制 MAPK/NF-κB 信号通路和减轻氧化应激减轻机械通气诱导的 COPD 大鼠肺损伤。
