【摘要】 目的评价甲泼尼龙对机械通气相关性肺损伤（VILI）大鼠肺泡内液体清除的影响。方法清洁级雄性SD大鼠60只,采用随机数字表法分为三组（n=20）:对照组（C组）、机械通气组（V组）和甲泼尼龙组（Mp组）。C组不行机械通气,自主呼吸空气4 h;Ⅴ组机械通气（RR40次/min,VT 40 mL/kg,I:E 1:1,PEEP 0,FiO₂ 21%）4 h;Mp组机械通气前20 min静注甲泼尼龙10 mg/kg。机械通气4 h时,取血标本和肺组织,测定肺湿/干质量（W/D）比值与肺通透指数（LPI）,观察肺组织病理学结果,测定肺泡内液体清除率（AFC）。Western blot法检测肺组织细胞外信号调节激酶（ERK）、磷酸化细胞外信号调节激酶（p-ERK）、肺泡上皮细胞钠离子通道（ENaC）、钠钾三磷酸腺苷酶（Na⁺-K⁺-ATPase）的表达水平。结果与C组比较,V组大鼠肺组织LPI和W/D比值升高[（2.17±0.07）×10^-3 vs.（6.46±0.31）×10-3,4.32±0.18 vs.8.74±0.53],AFC降低（%:30.56±5.35 vs.13.85±2.39）,p-ERK表达上调（0.51±0.03 vs.1.19±0.13）,ENaC和Na⁺-K⁺-ATPase表达下调（1.86±0.23 vs.0.71±0.08,1.82±0.21 vs.0.65±0.05）,P均<0.05,Mp组上述指标差异无统计学意义（P> 0.05）;与V组比较,Mp组大鼠肺组织LPI和W/D比值降低[（6.46±0.31）×10^-3 vs.（2.67±0.11）×10^-3,8.74±0.53 vs.4.77±0.21],AFC升高（%:13.85±2.39 vs.28.23±4.78）,p-ERK表达下调（1.19±0.13 vs.0.86±0.08）,ENaC和Na⁺-K⁺-ATPase表达上调（0.71±0.08 vs.1.71±0.18,0.65±0.05 vs.1.65±0.14）,P均<0.05。结论甲泼尼龙可通过促进肺泡内液体清除来减轻大鼠VILI,其机制与抑制ERK磷酸化,上调ENaC和Na⁺-K⁺-ATPase表达有关。更多还原

【Abstract】 Objective To evaluate the effect of methylprednisolone on alveolar fluid clearance（AFC） in the rats with mechanical ventilation-related lung injury（VILI）.Methods Sixty clean male SD rats were randomly divided into control group（group C,n=20）, mechanical ventilation group（group V,n=20） and methylprednisolone group（group Mp,n=20）.Group C did not undergo mechanical ventilation and breathed air independently for 4 hours;In group V,mechanical ventilation（RR 40 times/min,VT40 mL/kg,I:E 1:1,PEEP 0,FiO₂ 21%） lasted 4 hours;Methylprednisolone（10 mg/kg） was injected intravenously 20 minutes before mechanical ventilation in Mp group.At 4 hours after mechanical ventilation,blood samples and lung tissues were taken to determine the wet/dry weight ratio（W/D） and lung permeability index（LPI）,the pathological results of lung tissues were observed,and the intraalveolar fluid clearance（AFC） was measured.The expression levels of extracellular signal-regulated kinase（ERK）,phosphorylated extracellular signal-regulated kinase（p-ERK）,alveolar epithelial sodium channel（ENaC）,and sodium-potassium adenosine triphosphate（Na⁺-K⁺-ATPase） were tested by Western blot.Results Compared with group C,LPI,W/D ratio increased [（2.17±0.07） × 10^-3 vs.（6.46±0.31） × 10^-3,4.32±0.18 vs.8.74±0.53],AFC decreased（%:30.56±5.35 vs.13. 85±2.39）,p-ERK expression increased（0.51 ±0.03 vs.1.19±0.13）,ENaC and Na⁺-K⁺-ATPase expression decreased in group V（1.86±0.23 vs.0.71±0.08,1.82±0.21 vs.0.65±0.05）,All P<0.05.There was no significant difference in the above-mentioned indexes between group Mp and group C（P> 0.05）;Compared with group V,LPI,W/D ratio decreased [（6.46±0.31） x 10^-3 vs.（2.67±0.11） × 10^-3,8.74±0.53 vs.4.77 ±0.21],AFC increased（%:13.85 ± 2.39 vs.28.23± 4.78）,p-ERK expression decreased（1.19 ±0.13 vs.0.86±0.08）,ENaC and Na⁺-K⁺-ATPase expression increased in group Mp（0.71± 0.08 vs.1.71±0.18,0.65 ± 0.05 vs.1.65±0.14）,All P <0.05. Conclusion Methylprednisolone can alleviate VILI in rats by promoting AFC.The mechanism is related to the inhibition of ERK phosphorylation and up-regulation of ENaC and Na⁺-K⁺-ATPase expression.更多还原