任俊明　郭永清

[摘要] 目的 建立机械通气相关性肺损伤大鼠模型并进行评价，确定建立机械通气相关性肺损伤大鼠模型的最适通气条件。 方法 选取成年雄性SD大鼠72只，体重250～300 g，随机分为A、B、C、D组（n=18）：对照组（A 组，自主呼吸组），小潮气量（VT）组（B组，VT=6 ml/kg），常规VT组（C组，VT=10 ml/kg），大VT组（D组，VT=40 ml/kg），各组按机械通气时间（2、4、6 h）再随机分为3个亚组（n=6）。A组仅作气管切开插管，其余各组气管切开后接小动物呼吸机行机械通气，呼吸机参数均设置为RR 70/min，FiO2 21%，PEEP 0 cmH2O。机械通气结束后处死大鼠，剖胸取右肺组织计算湿重干重比（W/D），计算细胞凋亡指数，HE染色后光镜下观察肺组织病理学结果，并进行肺损伤评分。比较不同VT及通气时间条件下大鼠的肺损伤情况。 结果 与A、B、C组比较，D组通气2 h时开始出现肺损伤病理学表现，通气4 h时肺损伤评分、肺组织W/D和细胞凋亡指数均升高，差异有统计学意义（P<0.05）。 结论 给予大鼠40 ml/kg VT通气4 h可以成功建立机械通气相关性肺损伤模型。

[关键词] 机械通气相关性肺损伤；机械通气；动物模型；大鼠

[中图分类号] R332 [文献标识码] A [文章编号] 1674-4721（2016）02（c）-0011-04

[Abstract] Objective To establish and evaluate the rat model of ventilator-induced lung injury，and to determine the best ventilation condition of rat model of ventilator-induced lung injury. Methods 72 adult male SD rat were selected，weight was 250-300 g，and they were randomly divided into group A，B，C and D （n=18）.Control group （group A，spontaneous breathing group），low tidal volume group （group B，VT=6 ml/kg），routine tidal volume group （group C，VT=10 ml/kg） and high tidal volume group （group D，VT=40 ml/kg）.Each group was divided into 3 subgroups （n=6） according to duration of mechanical ventilation （2 h，4 h and 6 h）.group A was only given tracheotomy tube，the others were given small animal breathing machine to conduct mechanical ventilation after tracheotomy.The parameter of breathing machine was set as RR 70/min，FiO2 was 21%，PEEP was 0 cmH2O.The rat were sacrificed after the end of mechanical ventilation，W/D of right lung tissue taken by splitting chest was counted and cell apoptosis index was counted.The pathology results of lung tissue were observed under light microscope after HE staining.The score of lung damage was valued.Lung damage of rat at different tidal volume and duration of ventilation was compared. Results Compared with group A，B and C，lung damage pathology feature appeared after 2 h ventilation in group D and all of the lung damage score，W/D of lung tissue and cell apoptosis index was increased respectively，and the difference was statistical significance （P<0.05）. Conclusion Rat is given 40 ml/kg of tidal volume and ventilation for 4 h can establish the model of ventilator-induced lung injury successfully.

[Key words] Ventilator-induced lung injury；Mechanical ventilation；Animal model；Rat

机械通气（mechanical ventilation，MV）在危重患者的救治和麻醉维持过程中起重要作用，然而MV使用不当本身可以诱发严重肺损伤[1]。MV过程中较高的潮气量（VT）可以损害肺泡-毛细血管黏膜屏障，破坏肺组织内皮细胞和上皮细胞增加其通透性[2]，同时机械刺激导致肺泡内炎症细胞募集活化并释放炎症介质和细胞因子从而引起肺损伤[3]。目前，国内外肺损伤动物模型制备多选择鼠类、兔类、犬类、绵羊等动物，其中鼠类具有经济性、细胞生物学角色的可用性等优点使其在肺损伤模型建立研究中运用较多[4-5]。……