| 摘要: |
| 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2 ml/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1 mg/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300 mmHg(1 mmHg=0.133 kPa)以下，持续时间长达6 h；W/D于海水灌注后3 h达高峰，肺通透指数及肺病理评分以海水灌注后6 h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6 h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。 |
| 关键词: 海水 溺水 NF-κB 细胞因子类 急性肺损伤 |
| DOI：10.3724/SP.J.1008.2010.0394 |
| 投稿时间：2009-11-12修订日期：2010-03-06 |
| 基金项目:全军“十一五”科研计划课题(06-3305). |
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| Effects of dexamethasone on NF-κB activity in lung tissue of rabbits with seawater drowning-induced acute lung injury |
| RUI Meng, DUAN Yun-you*, WANG Hai-long, ZHANG Xin-hong, WANG Da-peng, HU Ming |
| (Department of Respiratory, Cadre Wards of General Hospital of Navy, Clinical Medical College of Navy, Second Military Medical University, Beijing 100048, China) |
| Abstract: |
| 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. |
| Key words: seawater drowning NF-κB cytokines acute lung injury |
