国际麻醉学与复苏杂志   2018, Issue (5): 4-4
    
右美托咪定对脂多糖诱导急性肺损伤大鼠肺泡液体清除的影响
姜远旭1()
1.深圳市人民医院
Effects of dexmedetomidine on alveolar fluid clearance in rats with acute lung injury induced by lipopolysaccharide
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摘要:

目的 研究右美托咪定(dexmedetomidine, Dex)对脂多糖(lipopolysaccharide, LPS)诱导的急性肺损伤(acute lung injury, ALI)大鼠肺泡内液体清除率(alveolar fluid clearance, AFC)的影响。 方法 健康雄性Wistar大鼠48只,按照随机数字表法将动物分为3组(每组16只):生理盐水对照组(NS组)、LPS模型组(LPS组)、Dex治疗组(LPS+Dex组)。采用静脉注射LPS复制ALI模型。NS组股静脉给予5 ml/kg生理盐水,即刻股静脉持续输注5 μg·kg-1·h-1生理盐水;LPS组股静脉给予10 mg/kg LPS,即刻股静脉持续输注5 μg·kg-1·h-1生理盐水;LPS+Dex组股静脉给予10 mg/kg LPS,即刻股静脉持续输注5 μg·kg-1·h-1 Dex;分别在注射LPS或生理盐水后6 h处死动物。血气分析检测PaO2,应用酶标仪读取Evans 蓝标记白蛋白的浓度测定AFC,H-E染色光镜下观察肺组织病理学变化,检测肺组织湿/干重比(wet/dry, W/D)、TNF-α、IL-1β的浓度及钠钾三磷酸腺苷酶(potassium sodium adenosine triphosphate enzyme, Na-K-ATPase)、肺泡上皮细胞钠离子通道(alveolar epithelial sodium channel, ENaC)的表达。 结果 与NS组比较,LPS组PaO2、AFC降低(P<0.01),W/D及TNF-α、IL-1β浓度升高(P<0.01),Na-K-ATPase、ENaC表达降低(P<0.01)。与LPS组比较,LPS+Dex组PaO2、AFC升高(P<0.01),W/D及TNF-α、IL-1β浓度降低(P<0.01),Na-K-ATPase、ENaC表达升高(P<0.01)。H-E染色显示,LPS组有明显的肺水肿,LPS+Dex组肺水肿减轻。 结论 Dex通过上调Na-K-ATPase、ENaC的表达,促进肺泡内液体清除,从而减轻LPS诱导的ALI大鼠肺水肿。

关键词: 右美托咪定; 急性肺损伤; 肺泡液体清除率; 钠钾三磷酸腺苷酶; 肺泡上皮细胞钠
Abstract:

Objective To investigate effects of dexmedetomidine(Dex) on alveolar fluid clearance (AFC) in rats with acute lung injury induced by lipopolysaccharide (LPS). Methods Forty-eight male Wistar rats were randomly divided into normal saline control (NS) group, LPS group, and Dex treatment (LPS+Dex) group. The rats in NS group were intravenously injected with 0.9% normal saline (5 ml/kg) followed by influsion of 0.9% normal saline (5 μg·kg-1·h-1). The rats in LPS group were intravenously injected with LPS (10 mg/kg) followed by influsion of 0.9% normal saline (5 μg·kg-1·h-1). The rats in LPS+Dex group were intravenously injected with LPS (10 mg/kg) followed by influsion of Dex (5 μg·kg-1·h-1). The rats were sacrificed 6 h after intravenous injection of LPS or NS, PaO2 was measured, AFC was determined by Evans blue-tagged albumin concentration changes. Histology of the lungs were assayed with H-E staining. The wet/dry weight ratio (W/D) of the lung was determined. The levels of TNF-α and IL-1β in the lung tissues were assessed by ELISA. The protein levels of potassium sodium adenosine triphosphate enzyme (Na-K-ATPase), alveolar epithelial sodium channel (ENaC) were detected by Western blot and immunohistochemistry. Results Compared with NS group, PaO2 was lower in LPS group, and this drop was reversed by Dex (in LPS+Dex group)(P<0.01). The W/D and the concentrations of TNF-α and IL-1β in the pulmonary tissues were increased in the LPS group, relative to the NS group, but the increases were compromised in the LPS+Dex group(P<0.01). AFC was reduced in LPS group, relative to NS group, but the reduction was compensat in LPS+Dex group(P<0.01). The expression of Na-K-ATPase and ENaC was lower in the LPS group than the NS group, but they were normalized in the LPS+Dex group(P<0.01). Conclusions Our findings suggest that dexmedetomidine may alleviate pulmonary edema by increasing AFC and the expression of Na-K-ATPase and ENaC in rats with acute lung injury induced by lipopolysaccharide.

Key words: Dexmedetomidine; Acute lung injury; Alveolar fluid clearance; Potassium sodium adenosine triphosphate enzyme; Alveolar epithelial sodium channel