目的:探讨艾氯胺酮对慢性阻塞性肺疾病(COPD)大鼠通气时炎症及氧化应激的影响。审查其监管机制。
方法:大鼠分为4组:对照组,COPD模型组(M),COPD模型加生理盐水治疗组(M+S),和COPD模型与艾氯胺酮治疗组(M+K),每组12只大鼠。两个月后,所有大鼠均接受麻醉和机械通气.M+K组静脉接受5mg/kg艾氯胺酮,而M+S组接受相同体积的生理盐水。两小时后收集肺组织进行分析,包括气道峰值压力,干湿比(W/D),肺通透性指数(LPI),苏木精和伊红(H&E)染色,和透射电子显微镜(TEM)。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),酶联免疫吸附试验(ELISA)检测白细胞介素-10(IL-10)水平;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氨基末端激酶(JNK),和磷酸化的JNK(p-JNK)表达通过蛋白质印迹和免疫组织化学;和丙二醛(MDA),髓过氧化物酶(MPO),和超氧化物歧化酶(SOD)水平也通过相应的生化测定来测量。
结果:来自M组的肺标本,M+S,M+K表现为COPD的标志性组织病理学特征。与Con组相比,M组显示气道峰值压力升高,W/D比,和LPI。M+K组,与M组相比,艾氯胺酮显著降低W/D比,LPI,和促炎细胞因子TNF-α的浓度,IL-6和IL-8同时升高IL-10水平。此外,治疗减弱了NF-κB和MAPK通路的激活,P-NF-κB水平降低,p-p38和p-JNK.此外,与M组相比,M+K组肺组织MDA、MPO水平降低,SOD水平升高。
结论:依维他明通过抑制MAPK/NF-κB信号通路和减轻氧化应激减轻COPD模型大鼠机械通气肺损伤。
OBJECTIVE: To investigate esketamine\'s impact on inflammation and oxidative stress in ventilated chronic obstructive pulmonary disease (COPD) rats, examining its regulatory mechanisms.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Esketamine attenuates mechanical ventilation-induced lung injury in COPD rat models by inhibiting the MAPK/NF-κB signaling pathway and reducing oxidative stress.