Gazi University, Faculty of Medicine, Department of Anesthesiology and Reanimation, Ankara, Turkey.
Gazi University, Faculty of Medicine, Department of Anesthesiology and Reanimation, Ankara, Turkey.
Braz J Anesthesiol. 2021 May-Jun;71(3):271-277. doi: 10.1016/j.bjane.2021.02.051. Epub 2021 Apr 15.
Sepsis is one of the leading causes of death in intensive care units. Dexmedetomidine is a sedative agent with anti-inflammatory properties. This study is designed to differentiate the impact of two different doses of dexmedetomidine on lung injury induced by sepsis.
Adult male Wistar rats were randomly divided into four groups: sham (n = 6), control (n = 12), 5DEX (n = 12), and 10DEX (n = 12). Cecal ligation puncture (CLP) was applied for sepsis initiation. The 5DEX group received 5 μg.kg.h and the 10DEX group received 10 μg.kg.h dexmedetomidine intravenous infusions for a 1-hour period. Six hours after CLP, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and intercellular adhesion molecule-1 (ICAM-1) levels were analyzed in blood samples. Twenty-four hours after CLP, lung samples from the remaining rats were collected for the measurement of myeloperoxidase (MPO) activity, histological examination, and TdT- (terminal deoxynucleotidyl transferase) mediated fluorescent-dUTP labeling staining for apoptosis detection.
Serum cytokine release, MPO activity, and apoptosis in the lung were significantly increased in the CLP group compared with the sham and dexmedetomidine groups (p < 0.05). TNF-α, ICAM-1, and MPO were significantly lower in the 10DEX group compared with both 5DEX and control groups, while IL-1β, total injury score, and apoptotic cell count had significantly lower values in both 10DEX and 5DEX groups compared with the control group (p < 0.05).
Dexmedetomidine administration played a protective role against CLP-induced lung injury. High-dose dexmedetomidine was needed for suppressing the leukocyte-mediated lung injury and apoptosis of lung tissue.
脓毒症是重症监护病房死亡的主要原因之一。右美托咪定是一种具有抗炎特性的镇静剂。本研究旨在区分两种不同剂量的右美托咪定对脓毒症诱导的肺损伤的影响。
成年雄性 Wistar 大鼠随机分为四组：假手术组（n=6）、对照组（n=12）、5DEX 组（n=12）和 10DEX 组（n=12）。采用盲肠结扎穿刺（CLP）建立脓毒症模型。5DEX 组给予 5μg·kg·h，10DEX 组给予 10μg·kg·h 右美托咪定静脉输注 1 小时。CLP 后 6 小时，分析血样中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和细胞间黏附分子-1（ICAM-1）水平。CLP 后 24 小时，收集其余大鼠的肺组织样本，用于测定髓过氧化物酶（MPO）活性、组织学检查以及 TdT-（末端脱氧核苷酸转移酶）介导的荧光-dUTP 标记染色以检测细胞凋亡。
CLP 组血清细胞因子释放、MPO 活性和肺组织细胞凋亡明显高于假手术组和右美托咪定组（p<0.05）。10DEX 组 TNF-α、ICAM-1 和 MPO 明显低于 5DEX 组和对照组，而 10DEX 组和 5DEX 组的 IL-1β、总损伤评分和凋亡细胞计数均明显低于对照组（p<0.05）。
右美托咪定给药对 CLP 诱导的肺损伤具有保护作用。高剂量右美托咪定可抑制白细胞介导的肺损伤和肺组织细胞凋亡。
