CAJ | 학술논문

目的探讨过氧化物酶体增殖物激活受体α激活剂--Wy14643对大鼠呼吸机相关性肺损伤的影响.方法健康雄性SD大鼠32只,随机分为4组(n=8):对照组(C组)、机械通气组(V组)、不同剂量Wy14643组(W1组和W2组).C组不行机械通气,其余3组均行大潮气量(VT40 ml/kg)机械通气2 h.W1组和W2组分别于机械通气前1 h经颈外静脉注射Wy14643(溶于10%二甲亚砜)1、3 mg/kg,C组和V组于机械通气前1 h经颈外静脉注射10%二甲亚砜1 ml/kg.于机械通气前、机械通气1、2 h时取股动脉血样行血气分析,计算PaO2/FiO2(氧合指数).通气2 h后收集支气管肺泡灌洗液(BALF)测定TNF-α和巨噬细胞炎症蛋白-2(MIP-2)的水平,取肺组织计算湿重/干重比(W/D比),取动脉血样,测定血清MDA、SOD水平,光镜下观察肺组织病理学.结果与C组比较,V组SOD水平降低,TNF-α、MIP-2、MDA的水平和W/D比升高(P＜0.05),肺组织病理学损伤明显;与V组比较,W1组和W2组氧合指数和SOD水平升高,TNF-α、MIP-2、MDA的水平和W/D比降低(P＜0.05),肺组织病理学损伤程度减轻.与W1组比较,W2组氧合指数和SOD水平升高,TNF-α、MIP-2、MDA的水平和W/D比降低(P＜0.05).结论 Wy14643可减轻大鼠呼吸机相关性肺损伤,且与剂量有关.
목적 탐토과양화물매체증식물격활수체α격활제--Wy14643대대서호흡궤상관성폐손상적영향.방법 건강웅성SD대서32지,수궤분위4조(n=8):대조조(C조)、궤계통기조(V조)、불동제량Wy14643조(W1조화W2조).C조불행궤계통기,기여3조균행대조기량(VT40 ml/kg)궤계통기2 h.W1조화W2조분별우궤계통기전1 h경경외정맥주사Wy14643(용우10%이갑아풍)1、3 mg/kg,C조화V조우궤계통기전1 h경경외정맥주사10%이갑아풍1 ml/kg.우궤계통기전、궤계통기1、2 h시취고동맥혈양행혈기분석,계산PaO2/FiO2(양합지수).통기2 h후수집지기관폐포관세액(BALF)측정TNF-α화거서세포염증단백-2(MIP-2)적수평,취폐조직계산습중/간중비(W/D비),취동맥혈양,측정혈청MDA、SOD수평,광경하관찰폐조직병이학.결과 여C조비교,V조SOD수평강저,TNF-α、MIP-2、MDA적수평화W/D비승고(P＜0.05),폐조직병이학손상명현;여V조비교,W1조화W2조양합지수화SOD수평승고,TNF-α、MIP-2、MDA적수평화W/D비강저(P＜0.05),폐조직병이학손상정도감경.여W1조비교,W2조양합지수화SOD수평승고,TNF-α、MIP-2、MDA적수평화W/D비강저(P＜0.05).결론 Wy14643가감경대서호흡궤상관성폐손상,차여제량유관.
Objective To investigate the effect of peroxisome proliferator-activated receptor α agonist Wy14643 on mechanical ventilation-induced lung injury in rats.Methods Thirty-two healthy male SD weighing 250-300 g were randomly divided into 4 groups(n = 8 each): group Ⅰ control(group C);group Ⅱ mechanical ventilation(group V)and group Ⅲ,Ⅳ pretreated with different doses of Wy14643(group W1 ,W2).The animals were anesthetized with intraperitoneal 3% pentobarbital 30 mg/kg and tracheostomized.The femoral artery and external jugular vein were cannulated for blood sampling and drug administration.Group C received no mechanical ventilation.In group V,W1 and W2 the animals were mechanically ventilated for 2 h(VT 40 ml/kg,RR40 bpm,I:E=1:2,FiO2 21%).In group W1 and W2 Wy14643 1 and 3 mg/kg were administered iv at 1 h before mechanical ventilation.Arterial blood samples were collected at 1 and 2 h of mechanical ventilation for determination of PaO2/FiO2.Serum SOD activity and MDA concentration were measured at the end of 2 h mechanical ventilation.The animals were then killed and the lungs removed for microscopic examination,lung lavage and W/D lung weight ratio.The MIP-2 and TNF-α concentrations in BALF were measured.Results Two hour mechanical ventilation significantly decreased serum SOD activity and increased serum MDA concentration,W/D lung weight ratio and TNF-α and MIP-2 concentrations in BALF as compared with group C.Wy14643 pretreatment significantly attenuated these mechanical ventilation-induced changes in group W1 and W2 in a dose-dependent manner.Conclusion Wy14643 can attenuate mechanical ventilation induced lung injury in rats and it is related to the dose.