CAJ | 학술논문

目的评价雷帕霉素联合罗格列酮对脓毒症大鼠肺损伤的影响.方法健康雄性Wistar大鼠120只,2月龄,体重250～ 300 g,采用随机数字表法,将其分为5组(n=24):假手术组(S组)、盲肠结扎穿孔组(CLP组)、雷帕霉素组(RPM组)、罗格列酮组(RGZ组)和雷帕霉素+罗格列酮组(RPM+ RGZ组).CLP组、RPM组、RGZ组和RPM+ RGZ组采用盲肠结扎穿孔术法制备大鼠脓毒症模型.术前30 min RPM组于皮下注射雷帕霉素0.4 mg/kg,RGZ组股静脉注射罗格列酮0.3 mg/kg,RPM+ RGZ组皮下注射雷帕霉素0.4 mg/kg联合股静脉注射罗格列酮0.3 mg/kg,CLP组给予等容量生理盐水.于术后2、6、24和48 h时分别处死6只大鼠,取肺组织,行HE染色,光镜下观察,进行肺损伤评分；采用分光光度法检测肺组织髓过氧化物酶(MPO)活性；采用凝胶阻滞电泳分析法检测肺组织信号转导和转录激活因子3(STAT3) DNA结合活性.结果与S组比较,CLP组、RPM组、RGZ组和RPM+ RGZ组肺损伤评分、肺组织MPO活性和STAT3 DNA结合活性升高(P＜0.05)；与CLP组比较,RPM组、RGZ组和RPM+ RGZ组肺损伤评分、肺组织MPO活性及STAT3 DNA结合活性降低(P＜0.05)；与RPM组及RGZ组比较,RPM+ RGZ组肺损伤评分、肺组织MPO活性及STAT3 DNA结合活性降低(P＜0.05).结论与雷帕霉素或罗格列酮单独用药比较,二者联合应用减轻脓毒症大鼠肺损伤的效应更明显,其机制与抑制STAT3信号通路激活有关.
목적 평개뢰파매소연합라격렬동대농독증대서폐손상적영향.방법 건강웅성Wistar대서120지,2월령,체중250～ 300 g,채용수궤수자표법,장기분위5조(n=24):가수술조(S조)、맹장결찰천공조(CLP조)、뢰파매소조(RPM조)、라격렬동조(RGZ조)화뢰파매소+라격렬동조(RPM+ RGZ조).CLP조、RPM조、RGZ조화RPM+ RGZ조채용맹장결찰천공술법제비대서농독증모형.술전30 min RPM조우피하주사뢰파매소0.4 mg/kg,RGZ조고정맥주사라격렬동0.3 mg/kg,RPM+ RGZ조피하주사뢰파매소0.4 mg/kg연합고정맥주사라격렬동0.3 mg/kg,CLP조급여등용량생리염수.우술후2、6、24화48 h시분별처사6지대서,취폐조직,행HE염색,광경하관찰,진행폐손상평분；채용분광광도법검측폐조직수과양화물매(MPO)활성；채용응효조체전영분석법검측폐조직신호전도화전록격활인자3(STAT3) DNA결합활성.결과 여S조비교,CLP조、RPM조、RGZ조화RPM+ RGZ조폐손상평분、폐조직MPO활성화STAT3 DNA결합활성승고(P＜0.05)；여CLP조비교,RPM조、RGZ조화RPM+ RGZ조폐손상평분、폐조직MPO활성급STAT3 DNA결합활성강저(P＜0.05)；여RPM조급RGZ조비교,RPM+ RGZ조폐손상평분、폐조직MPO활성급STAT3 DNA결합활성강저(P＜0.05).결론 여뢰파매소혹라격렬동단독용약비교,이자연합응용감경농독증대서폐손상적효응경명현,기궤제여억제STAT3신호통로격활유관.
Objective To evaluate the effects of rapamycin combined with rosiglitazone on lung injury in septic rats.Methods One hundred and twenty healthy male Wistar rats were randomly divided into 5 groups (n =6 each):sham operation group (group S); cecum ligation and punture (CLP) group; rapamycin group (group RPM) ; rosiglitazone group (group RGZ) ; rapamycin plus rosiglitazone group (group RPM + RGZ).The rats were anesthetized with intraperitoneal 10% chloral hydrate 100 mg/kg.Sepsis was induced by CLP in groups CLP,RPM,RGZ and RPM + RGZ.At 30 min before CLP,rapamycin 0.4 mg/kg was injected subcutaneously in RPM group,rosiglitazone 0.3 mg/kg was injected via the femoral vein in RGZ group,and rapamycin 0.4 mg/kg was injected subcutaneously and rosiglitazone 0.3 mg/kg was injected via the femoral vein in group RPM + RGZ.While the equal volume of normal saline was given instead in CLP group.Six rats were sacrificed at 2,6,24 and 48 h after CLP in each group,and lungs were removed and cut into sections which were stained with haematoxylin and eosin and examined under microscope.The pathological changes of lungs were scored.The myeloperoxidase (MPO) activity and signal transducer and activator of transcription 3 (STAT3)-DNA binding activity in lung tissues were measured.Results Compared with group S,the pathological scores,MPO activity and STAT3-DNA binding activity were significantly increased in groups CLP,RPM,RGZ,RPM + RGZ (P ＜ 0.05).The pathological scores,MPO activity and STAT3-DNA binding activity were significantly lower in groups RPM,RGZ and RPM +RGZ than in group CLP,and in group RPM + RGZ than in groups RPM and RGZ (P ＜ 0.05).Conclusion Rapamycin combined with rosiglitazone offers additional benefit to attenuating lung injury induced by sepsis over rapamycin or rosiglitazone alone,and inhibition of activation of STAT3 pathway is involved in the mechanism.