Qin Ming-Zhe, Gu Qiu-Han, Tao Jun, Song Xiao-Yang, Gan Guo-Sheng, Luo Zhong-Bin, Li Bi-Xi
Department of Anesthesiology, Wuhan General Hospital of Guangzhou Command Wuhan 430070, China.
Department of Anesthesiology, The 154 Hospital, People's Liberation Army Xinyang 464000, Henan Province, China.
Int J Clin Exp Pathol. 2015 Oct 1;8(10):12943-8. eCollection 2015.
Acute lung injury (ALI) is a common emergency and severe case in clinic. High mobility group protein box 1 (HMGB1) can be treated as a new anti-inflammatory treatment target. Toll-like receptor 4 (TLR4) is an important receptor of HMGB1. Ketamine is a widely used intravenous anesthetic with good anti-inflammatory and immune regulating function. Whether it can protect ALI through inhibiting HMGB1 and TLR4 expression in lung tissue still needs further investigation. Male SD rats were randomly divided into control, lipopolysaccharide (LPS) group and ketamine intervention group with 15 rats in each group. The rats were euthanatized at 24 h after modeling and the bronchoalveolar lavage fluid (BALF) was collected for HMGB1 and TLR4 level detection. Western Blot was applied to analyze HMGB1 and TLR4 protein expression in the lung tissue. HMGB1 and TLR4 concentration in BALF were 5.369 ± 1.564 ng/ml and 43.980 ± 7.524 pg/ml in the control, respectively. They were 12.358 ± 4.681 ng/ml and 102.538 ± 8.412 pg/ml in LPS group, and 7.399 ± 2.346 ng/ml and 87.208 ± 7.558 pg/ml in ketamine intervention group, respectively. Their levels increased significantly in LPS group and down-regulated after ketamine intervention. HMGB1 and TLR4 protein expression in lung tissue elevated obviously in LPS group, and decreased after ketamine treatment. HMGB1 and TLR4 protein level showed positive correlation in lung tissue (r = 0.921, P < 0.001). Ketamine can inhibit HMGB1 and TLR4 expression in ALI, and alleviate LPS induced rat lung injury.
急性肺损伤(ALI)是临床上常见的急症和重症。高迁移率族蛋白盒1(HMGB1)可被视为一种新的抗炎治疗靶点。Toll样受体4(TLR4)是HMGB1的重要受体。氯胺酮是一种广泛使用的静脉麻醉剂,具有良好的抗炎和免疫调节功能。它是否能通过抑制肺组织中HMGB1和TLR4的表达来保护ALI仍需进一步研究。雄性SD大鼠随机分为对照组、脂多糖(LPS)组和氯胺酮干预组,每组15只。造模后24小时处死大鼠,收集支气管肺泡灌洗液(BALF)检测HMGB1和TLR4水平。采用蛋白质免疫印迹法分析肺组织中HMGB1和TLR4蛋白表达。对照组BALF中HMGB1和TLR4浓度分别为5.369±1.564 ng/ml和43.980±7.524 pg/ml。LPS组分别为12.358±4.681 ng/ml和102.538±8.412 pg/ml,氯胺酮干预组分别为7.399±2.346 ng/ml和87.208±7.558 pg/ml。LPS组其水平显著升高,氯胺酮干预后下调。LPS组肺组织中HMGB1和TLR4蛋白表达明显升高,氯胺酮治疗后降低。肺组织中HMGB1和TLR4蛋白水平呈正相关(r = 0.921,P < 0.001)。氯胺酮可抑制ALI中HMGB1和TLR4的表达,并减轻LPS诱导的大鼠肺损伤。