甲泼尼龙对机械通气相关性肺损伤大鼠肺泡内液体清除的影响  

Effect of methylprednisolone on alveolar fluid clearance in the rats with mechanical ventilation-related lung injury

作　　者：瞿敏[1] 姚忠岩[1] 刘天琳 孙文波[1] 王娟[1] Qu Min;Yao Zhong-yan;Liu Tian-lin;Sun Wen-bo;Wang Juan(Department of Anesthesiology,Cangzhou Center Hospital,Cangzhou 061001,China)

机构地区：[1]沧州市中心医院麻醉科,河北沧州061001

出　　处：《中国急救医学》2020年第4期343-347,共5页Chinese Journal of Critical Care Medicine

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4h;V组机械通气(RR40次/min,VT 40 mL/kg,I∶E1∶1,PEEP0,FiO2 21%)4h;Mp组机械通气前20 min静注甲泼尼龙10 mg/kg.机械通气4h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.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,VT 40 miykg,I:E1:1,PEEPO,FiO221%)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^-3vs.(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)×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 pho

关 键 词：甲泼尼龙 机械通气相关性肺损伤(VILI) 肺泡内液体清除 细胞外信号调节激酶(ERK) 肺泡上皮细胞钠离子通道(ENac) 钠钾三磷酸腺苷酶(Na^+-K^+-ATPase) 

分 类 号：R563[医药卫生—呼吸系统]