酪氨酸蛋白激酶抑制剂对大鼠呼吸机所致肺损伤的保护作用

Protective action of inhibitors of protein tyrosine kinases on ventilator-induced lung injury

目的研究酪氨酸蛋白激酶抑制剂金雀异黄素(genistein)对大鼠呼吸机所致肺损伤(VILI)的保护作用。方法30只健康SD大鼠随机均分成A、B、C3组,A组为正常潮气量机械通气组:潮气量(VT)=8ml·kg-1;B组为大潮气量机械通气组:潮气量(VT)=40ml·kg-1;C组为大潮气量通气加Genistein处理组:潮气量(VT)=40ml·kg-1,C组大鼠实验前30min腹腔注射Genistein溶液(50mg·kg-1)。A、B、C3组机械通气频率(P)均为每分钟80次,通气时间均为2h。实验完毕收集肺组织和肺灌洗液标本。光镜观察肺病理改变,TUNEL法检测肺组织细胞凋亡情况,同时测定肺灌洗液中总蛋白、肺湿/干比、白细胞计数、肿瘤坏死因子(TNF-α)等指标以及肺组织中中性粒细胞髓过氧化物酶(MPO)的水平。结果和A组相比,B组肺病理改变明显,肺细胞凋亡数量增加,肺湿/干比、总蛋白、白细胞计数、MPO、TNF-α等指标均增高(P<0.01);和B组比较,C组肺病理改变明显减轻,肺细胞凋亡数量减少,肺湿/干比、总蛋白、白细胞计数、MPO、TNF-α等指标均降低(P<0.05)。结论酪氨酸蛋白激酶抑制剂genistein对大鼠呼吸机所致的肺损伤具有较好的保护作用。

Aim To study the protection of inhibitors of protein tyrosine kinases on ventilator-induced lung injury. Method Thirty healthy male SD rats were divided into three groups （A.B.C group, n = 10）. All groups performed mechanic ventilation. A group： tidal volume（ VT ） = 8 ml · kg^-1, breathing rate （ p ） = 80 breaths per minute （ bpm ） ; B group： tidal volume （ VT） = 40 ml · kg^ -1, breathing rate （p） = 80 bpm ; C grouptidal volume （VT） = 40 ml · kg^ -1 , breathing rate（p） = 80 bpm. All rats in C group were intraperitoneally injected genistein（50 mg ~ kg-1） 30 minutes before experiment. The time of ventilation in all groups was two hours. Rats were sacrificed and the lung lavage liquid and lung tissue with correct methods. The were collected and stored measured indexes include total protein, W/D, WBC, MPO and TNF-α. Lung pathological change was observed by microscope; Lung cell apoptosis was examined with TUNEL. Results Compared with A group, total protein, W/D, WBC, MPO, TNF-α and lung cell apoptosis significantly increased in B group（ P 〈 O. O1 ） ; Compared with B group, indexes above significantly decreased in C group（P 〈0. 05）. Conclusion Genistein may alleviate ventilator-induced lung injury.