CAJ | 학술논문

目的：探讨丙泊酚的肺保护作用及其可能作用机制。方法采用尾静脉注射内毒素建立急性肺损伤模型，丙泊酚和 LY294002同样经过尾静脉给药。将 Wistar 大鼠随机分入实验对照组（C 组）、脂多糖组（L 组）、脂多糖＋丙泊酚组（LP 组）和 LY294002组（LY 组）。每组16只，且每组随机选取8只进行肺泡Ⅱ型上皮细胞（ATⅡ）的分离。给药前及开始后第3、6和12 h 测定动脉血氧分压（PaO2），实验结束后观察肺湿／干重（W／D）比值、肺组织病理学检查并进行肺损伤轻重程度评分，同时观察各组大鼠 ATⅡ Akt 活性、Bax 蛋白表达及凋亡率。结果实验前各组 PaO2无明显差异，注射 LPS 后 L 组 PaO2持续下降，和 C 组相比其 PaO2显著降低（P ＜0．05）。实验结束后 L组和 C 组相比其 W／D 比值、肺组织病理学检查评分、ATⅡBax 蛋白表达及凋亡率显著升高（P ＜0．05），而 ATⅡAkt 活性显著降低（P ＜0．05）。而 LP 组和 L 组相比 W／D 比值、肺组织病理学检查评分、ATⅡBax 蛋白表达及凋亡率显著降低（P ＜0．05），而 PaO2和 ATⅡAkt 活性显著升高（P ＜0．05）。而 LY 组加入 LY294002后明显抑制丙泊酚以上保护作用。结论丙泊酚具有肺保护作用，且该作用可能与其通过激活 PI3K／Akt 通路而抑制 ATⅡ的过度凋亡作用相关。
목적：탐토병박분적폐보호작용급기가능작용궤제。방법채용미정맥주사내독소건립급성폐손상모형，병박분화 LY294002동양경과미정맥급약。장 Wistar 대서수궤분입실험대조조（C 조）、지다당조（L 조）、지다당＋병박분조（LP 조）화 LY294002조（LY 조）。매조16지，차매조수궤선취8지진행폐포Ⅱ형상피세포（ATⅡ）적분리。급약전급개시후제3、6화12 h 측정동맥혈양분압（PaO2），실험결속후관찰폐습／간중（W／D）비치、폐조직병이학검사병진행폐손상경중정도평분，동시관찰각조대서 ATⅡ Akt 활성、Bax 단백표체급조망솔。결과실험전각조 PaO2무명현차이，주사 LPS 후 L 조 PaO2지속하강，화 C 조상비기 PaO2현저강저（P ＜0．05）。실험결속후 L조화 C 조상비기 W／D 비치、폐조직병이학검사평분、ATⅡBax 단백표체급조망솔현저승고（P ＜0．05），이 ATⅡAkt 활성현저강저（P ＜0．05）。이 LP 조화 L 조상비 W／D 비치、폐조직병이학검사평분、ATⅡBax 단백표체급조망솔현저강저（P ＜0．05），이 PaO2화 ATⅡAkt 활성현저승고（P ＜0．05）。이 LY 조가입 LY294002후명현억제병박분이상보호작용。결론병박분구유폐보호작용，차해작용가능여기통과격활 PI3K／Akt 통로이억제 ATⅡ적과도조망작용상관。
ABSTRACT:Objective To investigate the protective effect of propofol on lung and its possible mechanism of action.Methods Acute lung injury(ALI)was induced by tail vein injection of en-dotoxin in Wistar rats.In addition,propofol and LY294002 were also injected via the caudal vein. Rats were randomly divided into four groups of 16 each:control group(group C),LPS group (group L),LPS+propofol group(group LP)and LY294002 group(group LY).Eight rats in each group were randomly selected to isolate alveolar epithelial type Ⅱ (ATⅡ)cells.The PaO2 was measured before and at 3,6 and 12 hours after administration.Lung wet/dry weight ratio and his-topathological score were measured at the end of experiment.At the same time,the Akt activity, Bax protein expression and apoptosis index were measured in ATⅡ cells.Results The were no significant differences in PaO2 among the four groups before administration.Compared with group C,the PaO2 decreased in group L after LPS injection,and wet/dry weight ratio and histopatholog-ical score of the lung and Bax expression and apoptosis index in ATⅡ cells increased but Akt ac-tivity reduced in group L at the end of experiment(P <0.05).Compared with group L,wet/dry weight ratio and histopathological score of the lung and Bax expression and apoptosis index in ATⅡ cells decreased but Akt activity increased in group L(P <0.05).However,the protective effect of propofol was significantly inhibited by treatment with LY294002 in LY group.Conclusion Propofol exertsprotective effect on lung,and the mechanism of action of propofol may involve the activation of PI3K/Akt pathway and the inhibition of excessive apoptosis in AT Ⅱ cells.