地塞米松对兔海水淹溺型急性肺损伤肺组织NF-κB活性改变的影响

Effects of dexamethasone on NF-κB activity in lung tissue of rabbits with seawater drowning-induced acute lung injury

目的探讨海水淹溺型急性肺损伤时NF-κB活性及TNF-α、IL-1β、IL-10等细胞因子表达量的改变以及地塞米松对其可能的影响。方法42只新西兰兔随机分成对照组(n=18)、模型组(n=12)和地塞米松治疗组(n=12)。模型组经气管插管灌注2ml/kg海水造成海水淹溺型急性肺损伤,地塞米松治疗组在造模同时经颈总动脉插管给予地塞米松1mg/kg。观察各组动物血气分析的动态变化,计算肺湿干质量比(W/D)、肺通透指数(LPI)。以非放射性凝胶迁移实验分析肺组织NF-κB活性,ELISA法检测肺组织TNF-α、IL-1β、IL-10浓度。H-E染色进行病理学检查,并计算肺病理评分(LPS)。结果与对照组比,模型组兔肺大体标本淤血水肿严重,体积明显增大,显微镜下可见炎性细胞浸润等急性肺损伤病理学征象;氧合指数迅速低至300mmHg(1mmHg=0.133kPa)以下,持续时间长达6h;W/D于海水灌注后3h达高峰,肺通透指数及肺病理评分以海水灌注后6h数值最高;肺组织NF-κB活性及TNF-α、IL-1β、IL-10等细胞因子表达量明显增高(P<0.05,P<0.01)。地塞米松治疗组病理学改变比对照组重,但比模型组轻;W/D、肺通透指数及肺病理评分也都比模型组低;氧合指数在海水灌注后6h亦得到明显改善;NF-κB活性及TNF-α、IL-1β、IL-10浓度均显著低于模型组(P<0.05,P<0.01)。结论地塞米松可抑制海水淹溺型急性肺损伤时肺组织NF-κB活性及TNF-α、IL-1β、IL-10等细胞因子的表达,减轻肺组织的炎症反应和病理损害。

Objective To explore the changes of nuclear factor-κB（NF-κB） activity,TNF-α,IL-1β and IL-10 contents in the lung tissue of rabbit with seawater drowning-induced acute lung injury（SWD-ALI） and the effects of dexamethasone on the changes.Methods Forty-two New Zealand white rabbits were randomly allocated to control group（C group,n = 18）,seawater drowning group（S group,n = 12） and dexamethasone treatment group（D group,n = 12）.The drowning model was established by instilling seawater（2 ml/kg body weight） into the endotracheal catheter of animals,then the rabbits received arterial injection of dexamethasone（D group,1 mg/kg body weight） or 2 ml normal saline（S group）.Blood gas analysis was done at predefined time points.The lung wet to dry weight ratio（W/D） and lung permeability index（LPI） were calculated.The activity of NF-κB was analyzed by non-radioactive electrophoretic mobility shift assay（EMSA）.The contents of TNF-α,IL-1β and IL-10 were detected by ELISA.Meanwhile,the pathology changes of lung tissues were detected by H-E staining,and the semi-quantitative lung pathologic scores（LPS） was also calculated.Results The lung of rabbits in S group was obviously enlarged and had more severe edema and congestion compared with C group;furthermore,histopathologic findings indicated inflammatory cell infiltration and other pathologic signs of ALI;the oxygenation index（PaO2 /FiO2） reached the bottom at 0.5 h and did not elevate to more than 300 mmHg（1 mmHg = 0.133 kPa） until 6 h.The largest W/D ratio appeared at 3 h after seawater drowning,and the highest LPI and LPS appeared at 6 h;and NF-κB activity and the contents of TNF-α,IL-1β and IL-10 in lung tissues were significantly higher in S group than in C group（P 0.05,P 0.01）.The pathological changes of lung in the rabbits of D group were improved compared with S group but worse than those of group C.The W/D ratio,lung permeability index,and lung pathological score in D group were lower than those of the S group;and the oxygenation index was greatly improved 6 h after seawater drowning.NF-κB activity and the contents of TNF-α,IL-1β and IL-10 in lung tissues were significantly lower than those of the S group（P 0.05,P 0.01）.Conclusion Dexamethasone can inhibit the activity of NF-κB and the expression of TNF-α,IL-1β and IL-10 in the lung tissue of rabbits with SWD-ALI and relieve the inflammatory responses and pathological changes.