Department of ICU, Affiliated Hospital of Weifang Medical College, Weifang, China.
Eur Rev Med Pharmacol Sci. 2018 Mar;22(6):1830-1836. doi: 10.26355/eurrev_201803_14603.
Inflammatory cytokines secretion is an important reason to promote lung tissue inflammation in acute lung injury (ALI). High mobility group box 1 (HMGB-1) and its receptor for advanced glycation end products (RAGEs) play a role in ALI. Ketamine can significantly alleviate ALI, whereas its specific mechanism has not been fully elucidated.
A total of 60 male Wistar rats were equally randomly divided into three groups, including ALI group which was established by 10 mg/kg LPS femoral vein injection, ketamine group which was constructed by 50 mg/kg ketamine femoral vein injection based on ALI model, and control group. Blood gas analysis was applied to detect arterial blood oxygen partial pressure (PaO2) and pH. Lung tissue wet/dry weight ratio (W/D), myeloperoxidase (MPO) and superoxide dismutase (SOD) activity were detected. Real-time PCR and ELISA were used to test HMGB-1 expression in lung tissue and serum. RAGE and NF-κB changes were determined by Real-time PCR and Western blot.
Compared with control, ALI group presented decreased PaO2 and PH, elevated W/D, enhanced MPO activity, declined SOD activity, upregulated HMGB-1 mRNA, increased HMGB-1 secretion, and increased RAGE and NF-κB mRNA and protein (p < 0.05). Ketamine treatment significantly elevated PaO2 and PH, reduced W/D, declined MPO activity, enhanced SOD activity, inhibited HMGB-1 mRNA and secretion, and downregulated RAGE and NF-κB mRNA and protein (p < 0.05).
Ketamine can alleviate LPS induced lung injury through inhibiting HMGB1-RAGE level. It could be treated as a new choice for ALI treatment.
炎症细胞因子的分泌是促进急性肺损伤（ALI）肺组织炎症的一个重要原因。高迁移率族蛋白 B1（HMGB-1）及其晚期糖基化终产物受体（RAGEs）在 ALI 中起作用。氯胺酮能显著缓解 ALI，但具体机制尚未完全阐明。
雄性 Wistar 大鼠 60 只，随机分为三组，每组 20 只，包括脂多糖（LPS）10mg/kg 股静脉注射建立的 ALI 组、基于 ALI 模型 50mg/kg 氯胺酮股静脉注射的氯胺酮组和对照组。血气分析检测动脉血氧分压（PaO2）和 pH 值。检测肺组织湿/干重比（W/D）、髓过氧化物酶（MPO）和超氧化物歧化酶（SOD）活性。实时 PCR 和 ELISA 检测肺组织和血清中 HMGB-1 的表达。通过实时 PCR 和 Western blot 检测 RAGE 和 NF-κB 的变化。
与对照组相比，ALI 组 PaO2 和 PH 值降低，W/D 升高，MPO 活性增强，SOD 活性降低，HMGB-1 mRNA 表达上调，HMGB-1 分泌增加，RAGE 和 NF-κB mRNA 和蛋白表达增加（p<0.05）。氯胺酮治疗后 PaO2 和 PH 值升高，W/D 降低，MPO 活性降低，SOD 活性升高，HMGB-1 mRNA 和分泌受抑制，RAGE 和 NF-κB mRNA 和蛋白表达下调（p<0.05）。
氯胺酮通过抑制 HMGB1-RAGE 水平缓解 LPS 诱导的肺损伤，可作为 ALI 的治疗新选择。
