丙戊酸钠对脂多糖诱导大鼠急性肺损伤的保护作用

摘要

目的 研究丙戊酸钠(valproic acid,VPA)对脂多糖(lipopolysaccharide,LPS)诱导的大鼠急性肺损伤的影响.方法 实验地点在武汉协和医院中心实验室,通过股静脉注射LPS复制大鼠急性肺损伤模型,观察光镜下肺组织病理学改变、血清炎性因子和肺部炎性反应判定模型是否成功.依据干预药物的不同确定实验分组:股静脉给予5mL/kg生理盐水为对照组(NS组),股静脉给予LPS 10 mg/kg为模型组(LPS组),模型成功后股静脉给予VPA 300mg/kg治疗为治疗组(LPS+VPA组).注射LPS或NS后6 h处死动物,血气分析观察动脉血氧分压(PaO2)、肺泡气-动脉血氧分压差(A-aDO2)、乳酸(Lac),检测肺组织干湿重比(W/D),髓过氧化物酶(MPO)活性,肺泡灌洗液(BALF)中白蛋白质量浓度,用ELISA法检测6 h血清中TNF-α和IL-1β的含量,HE染色光镜下观察肺组织病理学变化.计量资料以均数±标准差(-x±s)表示,应用SPSS 13.0统计软件行单因素方差分析.结果 LPS组PaO2(mmHg)(81.50±3.24)较NS组(106.40±4.50)降低,A-aDO2(mmHg),Lac[(19.70±2.21),(3.63±0.22)]较NS组[(6.30±1.70),(1.21±0.19)]升高,W/D,MPO活性(μ/g),BALF中白蛋白质量浓度(pg/mL)分别为[(6.52±0.30),(7.25±0.49),(2.940±0.047)]较NS组[(4.38±0.17),(1.76±0.31),(0.099±0.077)]升高,血清中TNF-α和IL-1β的质量浓度(pg/ml)分别为(3325±284),(1950±222)较NS组(90±12),(50±11)显著升高,差异具有统计学意义(P＜0.05),LPS组肺组织出现病理学改变;与LPS组比较,LPS+VPA组上述指标除PaO2(mmHg)(94.50±4.38)上升外,其余指标均降至[(13.50±4.77),(2.13±1.02),(5.33±0.12),(4.38±0.42),(1.260±0.039),(2410±320),(1220±162)],差异具有统计学意义(P＜0.05),LPS+VPA组肺组织病理学改变明显减轻.结论 丙戊酸钠对脂多糖诱导的大鼠急性肺损伤有一定保护作用.%Objective To investigate the effects of valproic acid (VPA) on acute lung injury induced by Lipopolysaccharide in rats. Method The rat model of acute lung injury was made by intravenous injection of lipopolysaccharide (LPS). The pathological changes of lung were observed under light microscope and inflammatory cytokines in serum detected by using ELISA to judge whether the model was successfully done or not. All rats were divided into three groups as per the different intervention agents employed. Rats in control group were treated with intravenous injection of NS in dose of 5 ml/kg, rats in LPS group were exposed to LPS with dosage of 10 mg/kg and model rats in LPS + VPA group were treated with VPA in dose of 300 mg/kg. The rats were sacrificed 6 h after LPS or NS administration. The blood PaO2 ,A-aDO2 and blood lactic acid (Lac) were measured, the lungs were removed for observing the histopathological changes and determination of wet/dry lung weight (W/D) ratio and myeloperoxidase (MPO) activity as well as albumin concentration in broncho-alveolar lavage fluid (BALF) . Seurm was collected to determine the concentrations of tumor necrosis factor-a (TNF-α) and interleukin-1β( IL-1 β) by using LISA 6 h later. All data were presented in ((x)±s). One-way ANOVA was used for comparing differences between groups. Results Compared with acute lung injury group, the blood PaO2 (94. 50 ± 4.38 ) in rats of LPS + VPA group was higher, whereas A-aDO2 ( 13.50 ± 4.77 ) and blood lac( 2.13 ± 1. 02 ) in LPS + VPA group were lower. VPA significantly lowered W/D (5.33 ±0. 12) ratio and MPO activity (4.38 ±0. 42) in the lung. Albumin concentration ( 1. 260 ± 0. 039 ) in BALF, and the levels of TN F-α( 2 410 ±320 )and IL-1β( 1 220 ± 162 )in serum were lower in LPS + VPA group. The histological changes of lung injury were lessened by VPA. Conclusions Valproic acid has protective effects against lipopolysaccharide-induced acute lung injury in rats.