建立小鼠烟雾吸入性损伤模型，观察烟雾吸入对小鼠肺肿瘤坏死因子-α(TNF-α)、内脏器官核转录因子-kappa B(NF-κB)及生存率的影响。

将190只BALB/c小鼠，随机选取10只，设为对照组；其余180只小鼠随机分为6组，每组30只，采用自制致伤装置，以松木屑和煤油作为发烟材料，对6组小鼠分别进行6、8、10、12、14、16 min烟雾吸入致伤，对照组小鼠不经烟雾吸入，其他处理同各烟雾吸入组。观察吸入性损伤后小鼠行为状态及72 h生存变化情况；各组小鼠死亡后立即取肺、心、肝、肾组织，观察其病理改变及检测组织细胞NF-κB活化状态积分值，并测定小鼠肺组织内TNF-α含量。数据间比较采用单因素方差分析及t检验。

(1)对照组，致伤6、8、10 min组小鼠在吸入致伤过程中均存活，而致伤12、14、16 min组小鼠在致伤过程中分别出现部分或全部死亡；除对照组外，各致伤组存活小鼠伤后出现呼吸急促、活动减少、随后自行恢复至正常状态；对照组，致伤6、8、10、12、14、16 min组伤后72 h生存率分别为100%、100%、97%、73%、52%、43%和0；(2)伤后死亡小鼠各器官组织有不同程度的炎症细胞浸润、充血、水肿等病理表现；(3)致伤14 min组伤后死亡的小鼠肺、心、肝、肾组织内可见大量位于细胞核中的NF-κB p65阳性染色，该阳性染色信号在伤后24～72 h时间段死亡小鼠上述器官组织的NF-κB p65蛋白积分光密度(IOD)值分别为3 245.37±296.40、2 022.92±356.52、2 148.70±310.99、2 054.61±260.56，均显著高于对照组，差异均有统计学意义(P值均小于0.05)；(4)致伤14 min组伤后24～72 h死亡小鼠的肺组织TNF-α的含量(54.86±5.24)pg/mL明显高于对照组(27.84±4.08)pg/mL、致伤时死亡(31.24±4.46)pg/mL及伤后0～24 h内死亡(45.09±4.69)pg/mL，差异均有统计学意义(P值均小于0.05)。

持续8～14 min烟雾吸入导致后续72 h内相应小鼠生存率下降、肺组织TNF-α表达显著上调以及多器官内的急性炎症反应和NF-κB信号通路的显著激活。烟雾吸入时间大于16 min时致小鼠即刻死亡。

To establish mice model of smoke inhalation injury, and observe the changes in the levels of lung tumor necrosis factor-alpha(TNF-α), the expressions of internal organ nuclear transcription factor-κB(NF-κB) and survival rate after smoke inhalation injury.

One hundred and niney BALB/c mice, randomly selected 10, set as the control group, the rest of the 180 mice were randomly divided into 6 groups, each group of 30. Adopting homemade injuries device, the mix of pine sawdust and kerosene was used as the fuming materials. The mice were subjected to smoke inhalation in a smoke chamber for different time intervals of 6, 8, 10, 12, 14, and 16 min, respectively, under anesthesia condition. The mice in the control group underwent the same treatment except for the inhalation of air only. Post-injury behavior changes and survivalrate at post-injury 72 h were documented, the tissue morphology changes and the NF-κB activation of multiple organs, presented by the integrated optical density (IOD), were evaluated. The expression of TNF-α in lung tissues was also determined. Data was compared using single factor analysis of variance and t test.

(1) The mice in the control group and 6, 8 and 10 min inhalation injury groups survived while several or all in 12, 14 and 16 min inhalation injury groups died in the smoking chamber during the smoke inhalation period. Except for the control group, increased respiratory rate and decreased activity were observed immediately after smoke inhalation injury in the live mice of each group and these abnormal signs were subsided several hours later. The survival rates at 72 h post-inhalation injury for the above control, 6, 8, 10, 12, 14 and 16 min smoke-inhalation groups were 100%, 100%, 97%, 73%, 52%, 43%, and 0, respectively; (2)Smoke inhalation induced varied extents of inflammatory cell infiltration, hyperemia, and swelling in tissues of multiple organs were observed in smoke inhalation-induced dead mice. (3)For 14 min smoke-inhalation injury group, the mice that died at post-injury 24-72 h demonstrated significantly enhanced positive nuclear expression of NF-κB p65 in cells of lung, heart, liver, and kidney tissues with higher IOD of NF-κB p65 expression of 3 245.37±296.40, 2 022.92±356.52, 2 148.70±310.99 and 2 054.61±260.56, respectively, in comparison with the control group(P values were less than 0.05); (4) For 14 min smoke-inhalation injury group, the level of TNF-α expression (54.86±5.24) pg/mL in lung tissues of mice that died during post-injury 24-72 h was significantly increased relative to that of the control group (27.84±4.08) pg/mL, death in the injury (31.24±4.46) pg/mL and death within 0-24 h after injury(45.09±4.69)pg/mL (P values were less than 0.05).

The 8-14 min duration of smoke inhalation leads to the proportional decline of mice 72-hour survival rate, significant up-regulation of TNF-α expression in lung tissues, acute inflammation and robust activation of NF-κB pathway in multiple organs. No mice survives the smoke inhalation for more than 16 minutes.