丙泊酚预处理通过活化PI3K／Akt通路减轻脂多糖诱导的大鼠急性肺损伤  

Propofol pretreatment attenuates LPS -induced acute lung injury in rats by activating phosphoinositide -3 -kinase/Akt pathway

作　　者：赵林林[1,2] 李俊芳[1] 朱珊珊[1] 刘功俭[1,2] 

机构地区：[1]徐州医学院江苏省麻醉学重点实验室,江苏徐州221002 [2]徐州医学院附属医院麻醉科,江苏徐州221002

出　　处：《徐州医学院学报》2012年第1期1-5,共5页Acta Academiae Medicinae Xuzhou

摘　　要：目的 研究丙泊酚预处理对脂多糖诱导的大鼠急性肺损伤（ALI）是否有保护作用,这种保护作用是否和活化PI3K/Akt通路有关.方法 36只成年雄性SD大鼠被随机分为6组（n＝6）：对照组（control组）、脂多糖（LPS）组、丙泊酚＋LPS组、Wortmannin＋丙泊酚＋LPS组、丙泊酚组、Wortnannin组.检测各组大鼠支气管肺泡灌洗液（BALF）中蛋白、TNF-α和IL-6浓度,观察各组大鼠的肺水含量和肺组织的病理变化,以及肺组织中p-Akt的表达变化.另取36只大鼠,随机分为3组（n＝12）：LPS组、丙泊酚＋LPS组和Wortmannin＋丙泊酚＋LPS组,建立大鼠ALI模型,观察各组大鼠48 h的死亡率.结果 注射LPS后,大鼠BALF中的蛋白、TNF-α和IL-6的浓度明显升高,肺水含量显著增加（P＜0.05）,肺组织破坏明显,肺组织中p-Akt表达减少.丙泊酚预处理降低肺组织损伤程度,使BALF中的蛋白渗出、TNF-α和IL-6释放减少（P＜0.05）,肺水含量以及肺组织的病理损害减轻,肺组织p-Akt表达增多（P＜0.05）.Wortmannin可减弱丙泊酚的保护作用,且单独使用Wortmannin对肺组织没有损害作用.丙泊酚＋LPS组死亡率明显低于LPS组和Wortmannin＋丙泊酚＋LPS组（P＜0.05）.结论 丙泊酚预处理可能通过诱导肺组织p-Akt表达,提高肺实质细胞对伤害刺激的耐受力,缓解LPS诱导的急性肺损伤.Objective To investigate the role of PI3k/Akt signal pathway in the protective effect of propofol pretreatment in LPS - induced acute lung injury in rats. Methods Healthy adult male SD rats were randomly divided into 6 groups （ n = 6 each ） ： Control group, LPS group, propofol ＋ LPS group, Wortmannin ＋ propofol ＋ LPS group, propofol group, Wortmannin group. The concentrations of protein,tumor necrosis factor - α （ TNF - α） and interleukin - 6（ IL - 6 ） in bronchoalveolar lavage fluids（BALF） were detected. The histopathologic changes of lung tissues by hematoxylin - eosin staining and the lung water content changes were also observed. To explore the mechanisms, the expression of p - Akt in lung tissues were analysed by Western blot. Further,to confirm the role of propofol in this model, another thirty - six rats were divided into three groups （n = 12 each） for survival study： LPS group, propofol ＋ LPS group and Wortmannin ＋ propofol ＋ LPS group, treated as mentioned above and were observed for 48 hours. Results With the administration of LPS, the protein and cytokines in BALF were significantly increased, the lung tissues showed obvious inflammatory respon- ses under light microscopy and the lung water content was significantly increased （ P 〈 0.05 ）. Simultaneously, the expressions of p - Akt were substantially decreased immediately. Pretreatment with propofol in vivo effectively attenuated the lung injury ,the concentrations of protein, TNF-α and IL- 6 in BALF significantly decreased （P 〈 0.05 ） , the lung water con- tent was reduced and the histopathologie changes of lung tissues were relieved obviously. Furthermore, the expressions of p -Akt were substantially increased （P 〈0. 05）. But Wortmannin weaken its protective effect, and there was no lung injury with Wortmannin abusing alone. Propofol pretreatment significantly decreased the LPS - induced lethality （ P 〈 0.05 ）, but Wortmannin weaken its protective effect （P 〈 0.05 ）. Conclusion Pro

关 键 词：AKT 丙泊酚 脂多糖 急性肺损伤 大鼠 

分 类 号：R971.2[医药卫生—药品]