CAJ | 학술논문

目的评价洛沙坦对糖尿病小鼠机械通气相关肺损伤的影响.方法 SPF级雌性C57/BL6小鼠48只,10 ～ 12周龄,体重20 ～ 25 g,采用随机数字表法,将小鼠随机分为3组(n=16)∶对照组(C组)、糖尿病机械通气组(DM组)和洛沙坦组(L组).DM组和L组采用腹腔注射链脲佐菌素150mg/kg的方法制备糖尿病模型.取糖尿病模型制备成功的小鼠进行机械通气4h,吸入氧浓度50％,通气频率70次/min,潮气量15 ml/kg,PEEP 2 cm H2O.L组于机械通气前30 min腹腔注射洛沙坦30mg/kg.机械通气4h时采集颈动脉血样,测定PaO2,随后处死,取肺组织,测定湿/干重比(W/D比)、髓过氧化物酶(MPO)活性和肺微血管通透性；采用实时荧光定量RT-PCR法测定血管紧张素Ⅱ(AngⅡ)受体AT1 mRNA的表达水平；ELISA法测定AngⅡ的含量；Western blot法测定细胞核内NF-κB p65的表达水平.结果与C组比较,DM组和L组PaO2降低,肺组织W/D比、MPO活性、肺微血管通透性和AngⅡ含量升高,AT1 mRNA和NF-κB p65表达上调(P＜0.05)；与DM组比较,L组PaO2升高,肺组织W/D比、MPO活性、肺微血管通透性和Ang Ⅱ含量降低,AT1 mRNA和NF-κB p65表达下调(P＜0.05).结论洛沙坦通过抑制AT1受体和Ang Ⅱ水平,从而改善肺微血管通透性和抑制NF-κB活化,减轻糖尿病小鼠机械通气相关肺损伤.
목적 평개락사탄대당뇨병소서궤계통기상관폐손상적영향.방법 SPF급자성C57/BL6소서48지,10 ～ 12주령,체중20 ～ 25 g,채용수궤수자표법,장소서수궤분위3조(n=16)∶대조조(C조)、당뇨병궤계통기조(DM조)화락사탄조(L조).DM조화L조채용복강주사련뇨좌균소150mg/kg적방법제비당뇨병모형.취당뇨병모형제비성공적소서진행궤계통기4h,흡입양농도50％,통기빈솔70차/min,조기량15 ml/kg,PEEP 2 cm H2O.L조우궤계통기전30 min복강주사락사탄30mg/kg.궤계통기4h시채집경동맥혈양,측정PaO2,수후처사,취폐조직,측정습/간중비(W/D비)、수과양화물매(MPO)활성화폐미혈관통투성；채용실시형광정량RT-PCR법측정혈관긴장소Ⅱ(AngⅡ)수체AT1 mRNA적표체수평；ELISA법측정AngⅡ적함량；Western blot법측정세포핵내NF-κB p65적표체수평.결과 여C조비교,DM조화L조PaO2강저,폐조직W/D비、MPO활성、폐미혈관통투성화AngⅡ함량승고,AT1 mRNA화NF-κB p65표체상조(P＜0.05)；여DM조비교,L조PaO2승고,폐조직W/D비、MPO활성、폐미혈관통투성화Ang Ⅱ함량강저,AT1 mRNA화NF-κB p65표체하조(P＜0.05).결론 락사탄통과억제AT1수체화Ang Ⅱ수평,종이개선폐미혈관통투성화억제NF-κB활화,감경당뇨병소서궤계통기상관폐손상.
Objective To evaluate the effect of losartan on mechanical ventilation-induced lung injury in diabetic mice.Methods Forty-eight female SPF C57/BL6 nice,aged 10-12 months,weighing 20-25 g,were randomly assigned into 3 groups (n =16 each):control group (group C).,diabetes + mechanical ventilation (group DM) and losartan group (group L).Diabetes mellitus was induced by intraperitoneal streptozotocin 150 mg/kg and confirmed by blood glucose level ＞ 16 mmol/L in groups DM and L.Diabetic mice were mechanically ventilated (FiO250％,VT 15 ml/kg,RR 70 bpm,PEEP 2 cm H2O) for4 h.Losartan 30 mg/kg was injected intraperitoneally 30 min before ventilation in group L.Eight mice from each group were chosen at 4 of ventilation and arterial blood samples were obtained for detection of PaO2.The animals were then sacrificed and the lungs were removed for determination of W/D lung weight ratio,myeloperoxidase (MPO) activity,pulmonary microvascular permeability,angiotensin Ⅱ (Ang Ⅱ) receptor AT1 mRNA expression (by RT-PCR),Ang Ⅱ content and nuclear factor kappa B (NF-κB) p65 expression (by Western blot).Results Compared with group C,PaO2 was significantly decreased,while W/D lung weight ratio,MPO activity,pulmonary microvascular permeability and Ang Ⅱ content were significantly increased,and the expression of AT1 mRNA and NF-κB p65 was up-regulated in groups DM and L (P ＜ 0.05).PaO2 was significantly higher,and W/D lung weight ratio,MPO activity,pulmonary microvascular permeability,Ang Ⅱ content and the expression of AT1 mRNA and NF-κB p65 were significantly lower in group L than in group DM (P ＜ 0.05).Conclusion Losartan can reduce mechanical ventilation-induced lung injury in diabetic mice through inhibiting AT1 receptor and Ang Ⅱ levels and improving pulmonary microvascular permeability and inhibiting NF-κB activation.