CAJ | 학술논문

目的比较雾化吸入和静脉注射米力农对大鼠急性肺损伤(ALI)的疗效.方法 SD大鼠40只,体重300～350 g,随机分为4组(n=10):对照组(Ⅰ组)、ALI组(Ⅱ组)、米力农雾化吸入组(Ⅲ组)和米力农静脉注射组(Ⅳ组).Ⅰ组经右颈外静脉插管注入0.1%BSA溶液2 ml/kg;Ⅱ组经20 min注入油酸混悬液2 ml/kg;Ⅲ组注入油酸后30 min雾化吸入1 mg/ml米力农10 min,每60分钟重复一次,共4次;Ⅳ组注入油酸后30 min经右颈外静脉注射米力农10 μg/kg,然后静脉输注米力农1 μg·kg-1·min-1 10min,每60分钟重复一次,共4次.各组于第4次治疗结束后放血处死大鼠.于治疗开始即刻、第1次治疗时、第2次治疗时、第3次治疗时和第4次治疗时,记录平均动脉压(MAP)和肺动脉压(PAP),测定动脉血气和混合静脉血气,计算氧合指数(PaO2/FiO2)和肺内分流率(Qs/Qt).回收支气管肺泡灌洗液(BALF),进行中性粒细胞计数,采用Bradford法测定蛋白浓度;测定肺组织湿,干重比(W/D)和髓过氧化物酶(MPO)活性;观察肺组织超微结构.结果与Ⅲ组比较,Ⅳ组第3次治疗和第4次治疗时MAP和Pa02/FiO2降低,第4次治疗时PAP和Qs/Qt升高,BALF蛋白浓度、中性粒细胞计数和肺组织W/D、MPO活性均升高(P＜0.05).结论雾化吸入米力农减轻大鼠ALI的作用优于静脉注射米力农,对血液动力学影响小.
목적 비교무화흡입화정맥주사미력농대대서급성폐손상(ALI)적료효.방법 SD대서40지,체중300～350 g,수궤분위4조(n=10):대조조(Ⅰ조)、ALI조(Ⅱ조)、미력농무화흡입조(Ⅲ조)화미력농정맥주사조(Ⅳ조).Ⅰ조경우경외정맥삽관주입0.1%BSA용액2 ml/kg;Ⅱ조경20 min주입유산혼현액2 ml/kg;Ⅲ조주입유산후30 min무화흡입1 mg/ml미력농10 min,매60분종중복일차,공4차;Ⅳ조주입유산후30 min경우경외정맥주사미력농10 μg/kg,연후정맥수주미력농1 μg·kg-1·min-1 10min,매60분종중복일차,공4차.각조우제4차치료결속후방혈처사대서.우치료개시즉각、제1차치료시、제2차치료시、제3차치료시화제4차치료시,기록평균동맥압(MAP)화폐동맥압(PAP),측정동맥혈기화혼합정맥혈기,계산양합지수(PaO2/FiO2)화폐내분류솔(Qs/Qt).회수지기관폐포관세액(BALF),진행중성립세포계수,채용Bradford법측정단백농도;측정폐조직습,간중비(W/D)화수과양화물매(MPO)활성;관찰폐조직초미결구.결과 여Ⅲ조비교,Ⅳ조제3차치료화제4차치료시MAP화Pa02/FiO2강저,제4차치료시PAP화Qs/Qt승고,BALF단백농도、중성립세포계수화폐조직W/D、MPO활성균승고(P＜0.05).결론 무화흡입미력농감경대서ALI적작용우우정맥주사미력농,대혈액동역학영향소.
Objective To compare the therapeutic effect of inhaled aerosolized and intravenous milrinone,a phosphodiesterase-3 inhibitor in rats with oleic acid-induced acute lung injury (ALI) .Methods Forty male SD rats weighing 300-350 g were randomly divided into 4 groups (n=10 each) : group Ⅰ normal control: group Ⅱ ALI; group Ⅲ milfinone inhalation and group Ⅳ intravenous milrinone.The animals were anesthetized with intraperitoneal 2% pentobarbital 40 mg/kg,tracheostomized and mechanically ventilated (FiO2 30%,VT 10 ml/kg,RR 80 bpm,I:E=1:2).The chest was opened and the heart was exposed.Pulmonary artery was catheterized via fight ventricle.MAP,CVP,airway pressure and pulmonary artery pressure (PAP) were monitored.ALI was induced with 10% oleic acid 2 ml/kg administered through fight external jugular vein in group Ⅱ,Ⅲ and Ⅳ.In control group 0.1% BSA solution 2 ml/kg was administered iv instead of oleic acid.In group Ⅲ at 30 min after oleic acid administration aerosolized milrinone 1 mg/ml was inhaled 4 times at 60 min interval.Each time milrinone was inhaled for 10 min.In group Ⅳ at 30 min after oleic acid administration a bolus of 10 μg/kg milrinone was given iv followed by 10 min milrinone infusion at 1 μ·kg-1·min-1.The same procedure was repeated 4 times at 60 min interval.MAP and PAP were recorded and blood samples were taken from carotid artery and pulmonary artery for blood gas analysis at the 1st,2nd,3rd and 4th treatment.PaO2/FiO2 and Qs/Qt were calculated.The animals were sacrificed by exsanguination after the 4th treatment.The lungs were removed.The left lung was lavaged.Neutrophil count and protein content in broncho-alveolar lavage fluid (BALF) were determined.W/D lung weight ratio and lung myeloperoxidase (MPO) activity were measured.The uhrastructure of the lung was examined with electron microscope.Results The MAP was significantly lower after oleic acid adminstration in group Ⅳ than in other 3 groups.PaO2/FiO2 was significantly decreased and Qs/Qt increased by iv oleic acid in group Ⅱ ,Ⅲ and Ⅳ.PAP was significantly increased after iv oleic acid in group Ⅱ ,Ⅲ and Ⅳ but was significantly lower in group Ⅲ and Ⅳ than in group Ⅱ .The neutrophil count and total protein content in BALF,W/D ratio and lung MPO activity were significantly increased in group Ⅱ ,Ⅲ and Ⅳ as compared with control group(Ⅰ) and were significantly higher in group Ⅳ than in group Ⅲ.The lung damage induced by oleic acid was less serious in group Ⅲ and Ⅳ than in group Ⅱ .Conclusion Inhaled aerosoLized milrinone has better therapeutic effect than intravenous milrinone in rats with oleic acid-induced ALI and is safer.