CAJ | 학술논문

目的探讨盐酸戊乙奎醚对胸部创伤-失血性休克复苏致大鼠急性肺损伤时Fas/FasL表达的影响.方法 SPF级健康雄性SD大鼠30只,体重245～ 275 g,8周龄,采用随机数字表法分为3组(n=10):假手术组(Sham组)、胸部撞击-失血性休克复苏组(THSR组)和盐酸戊乙奎醚组(PHCD组).建立胸部撞击-失血性休克复苏致急性肺损伤模型:将砝码(300 g)于95 cm高处自由落体,撞击大鼠心前区,5 min后经股动脉放血,使MAP在15 min内降至35～ 45 mmHg,并维持60min,然后进行复苏.PHCD组于失血性休克60 min时静脉注射盐酸戊乙奎醚2 mg/kg.于模型制备成功后6h放血处死大鼠,取肺组织,观察病理学结果,采用Western blot法和免疫组化SABC法检测Fas、FasL和caspase-8的表达,采用TUNEL法检测肺组织细胞凋亡指数(AI),采用ELISA法测定肺组织IL-6和IL-1β含量.结果与Sham组比较,THSR组和PHCD组肺组织Fas、FasL和caspase-8表达上调,AI升高,IL-6和IL-1β含量升高(P＜0.05);与THSR组比较,PHCD组肺组织Fas、FasL和caspase-8表达下调,AI降低,IL-6和IL-1β含量降低(P＜0.05).PHCD组肺组织病理学损伤较THSR组明显减轻.结论盐酸戊乙奎醚抑制胸部创伤-失血性休克复苏诱发的大鼠肺组织细胞凋亡的机制与抑制Fas/FasL表达有关.
목적 탐토염산무을규미대흉부창상-실혈성휴극복소치대서급성폐손상시Fas/FasL표체적영향.방법 SPF급건강웅성SD대서30지,체중245～ 275 g,8주령,채용수궤수자표법분위3조(n=10):가수술조(Sham조)、흉부당격-실혈성휴극복소조(THSR조)화염산무을규미조(PHCD조).건립흉부당격-실혈성휴극복소치급성폐손상모형:장겁마(300 g)우95 cm고처자유락체,당격대서심전구,5 min후경고동맥방혈,사MAP재15 min내강지35～ 45 mmHg,병유지60min,연후진행복소.PHCD조우실혈성휴극60 min시정맥주사염산무을규미2 mg/kg.우모형제비성공후6h방혈처사대서,취폐조직,관찰병이학결과,채용Western blot법화면역조화SABC법검측Fas、FasL화caspase-8적표체,채용TUNEL법검측폐조직세포조망지수(AI),채용ELISA법측정폐조직IL-6화IL-1β함량.결과 여Sham조비교,THSR조화PHCD조폐조직Fas、FasL화caspase-8표체상조,AI승고,IL-6화IL-1β함량승고(P＜0.05);여THSR조비교,PHCD조폐조직Fas、FasL화caspase-8표체하조,AI강저,IL-6화IL-1β함량강저(P＜0.05).PHCD조폐조직병이학손상교THSR조명현감경.결론 염산무을규미억제흉부창상-실혈성휴극복소유발적대서폐조직세포조망적궤제여억제Fas/FasL표체유관.
Objective To investigate the effects of penehyclidine hydrochloride on Fas/FasL expression during acute lung injury induced by blunt chest trauma-hemorrhagic shock and resuscitation (HSR) in rats.Methods Thirty male SPF Sprague-Dawley rats, aged 8 weeks, weighing 245-275 g, were randomly assigned into 3 equal groups using a random number table: sham operation group (group Sham) , blunt chest trauma-HSR group (group THSR) and penehyclidine hydrochloric group (group PHCD).The model of acute lung injury induced by blunt chest trauma-HSR was induced by dropping a 300 g weight onto a precordium in anesthetized rats.Blood was withdrawn via the femoral artery 5 min later until mean arterial pressure was decreased to 35-45 mmHg within 15 min, and maintained at this level for 60 min, followed by resuscitation.In PHCD group, PHCD 2 mg/kg was injected intravenously at 60 min after hemorrhagic shock.At 6 h after the model was established, the rats were sacrificed, the lungs were then removed for microscopic examination of pathologic changes and for determination of Fas, FasL and caspase-8 expression, and interleukin-6 (IL-6) and IL-1β contents in lung tissues.Apoptotic index was calculated.Results Compared with group Sham, the expression of Fas, FasL and caspase-8 was significantly up-regulated, and AI and contents of IL-6 and IL-1β were increased in THSR and PHCD groups (P＜O.05).Compared with group THSR, the expression of Fas, FasL and caspase-8 was significantly down-regulated,and AI and contents of IL-6 and IL-1β were decreased in group PHCD (P＜0.05).The pathologic changes of lungs were significantly reduced in group PHCD compared with group THSR.Conclusion The mechanism by which penehyclidine hydrochloride inhibits lung cell apoptosis induced by blunt chest trauma-HSR is associated with inhibition of Fas/FasL expression in rats.