摘要
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12h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ATⅡAkt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。
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 endotoxin in Wistar rats.In addition,propofol and LY294002 were also injected via the caudal vein.Rats were randomly divided into four groups of 16each：control group（group C）,LPS group（group L）,LPS＋propofol group（group LP）and LY294002group（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 3,6and 12 hours after administration.Lung wet/dry weight ratio and histopathological 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 histopathological score of the lung and Bax expression and apoptosis index in ATⅡ cells increased but Akt activity 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.
出处
《南昌大学学报（医学版）》
CAS
2014年第11期4-7,18,F0003,共6页
Journal of Nanchang University：Medical Sciences
基金
江西省青年科学基金资助项目(No.2011ZBAB214024)
