抑制PTEN在小鼠内毒素性肺损伤中的作用

Role of PTEN inhibition in LPS-induced acute lung injury in mice

目的探讨抑制同源物基因（PTEN）在小鼠内毒素（LPS）性急性肺损伤中的作用。方法C57BL／6小鼠，8～10周龄，随机分为4组：对照组（control组，n=6）、LPS组（n=12）、Wortmannin＋LPS组（n=12）和Phen＋LPS组（／t=12）。对照组气管内滴人等体积生理盐水，Wortmannin＋LPS组和Phen＋LPS组腹腔注射Wortmannin 0．6mg／kg和Phen1．6μmoL／kg．1h后气管内滴入LPS 5mg／kg，LPS组气管内滴入LPS 5mg／kg。注射脂多糖或生理盐水后6h时处死动物，取肺组织，光镜下观察病理学结果，进行肺损伤评分、肺组织湿重／干重比值（W／D比值），以及肺系数、肺水含量、肺通透指数、肺血管通透性、血气分析指标的测定。结果Phen＋LPS组的肺损伤评分、肺组织W／D比值、肺系数、肺水含量、肺通透指数、PCO2均显著低于LPS组（P〈0．05），但高于对照组（P〈0．05）。与Wortmannin＋LPS组比较．肺损伤评分、肺组织W／D比值、肺系数、肺水含量、肺通透指数、PCO2和病理评分均显著降低（P〈0.01）。结论抑制PTEN可降低肺水肿参数，降低肺血管通透性。

Objective To investigate the role of inhibition of the PTEN in LPS-induced acute lung injury in mice. Methods 42 C57BL/6 mice, aged 8-10 weeks, were randomly divided into four groups as follows：control group （n=6）, LPS group （n=12）, Phen＋LPS group （n=12） and Wortmannin＋LPS group （n=12）. In control group, the equal volume of normal saline was given via the intratracheal instillation. In Phen＋LPS group and Wortmannin＋LPS group, Phen 1.6 Ixmol/kg and Wortmannin 0.6 mg/kg were given respectively by intraperitoneal injection. And 60 min later, lipopo lysaecharide （LPS） 5 mg/kg was injected via the intratracheal instillation in Phen＋LPS group and Wortmannin＋LPS group, while the equal volume of LPS was given in LPS group. The mice were sacrificed at 6 h after LPS or normal saline injection. The lung was immediately removed for microscopic examination and for determination of wet/dry lung weight ratio （W/D ratio）, the levels of lung index, lung water, lung penetrating index （LPL） and lung vasopermeability. The arterial blood gas was analysed and the pathological changes of the lung were scored. Results Compared with LPS group, the lung injury scores, W/D ratio, lung index, lung water, lung penetrating, PCO2 and pathology score in Phen＋ LPS group decreased significantly （P 〈 0.05）, but higher than those in control group （P 〈 0.05）. Those in Phen＋LPS group decreased significantly in comparison with Wortmannin＋LPS group （P 〈 0.01）. Conclusion Inhibition of the PTEN has protective effects on pulmonary vascular permeability in LPS-induced acute lung injury.