乌司他丁对水下爆炸所致兔急性肺损伤的保护作用

Effect of ulinastatin on acute lung injury induced by underwater explosion in rabbits

目的 观察乌司他丁对水下爆炸所致兔急性肺损伤(ALI)的保护作用,并探讨其作用机制。方法 将健康清洁新西兰兔40只按随机数字表法分为正常对照组(N)、模型组(A)、低剂量治疗组(B)、高剂量治疗组(C),每组10只。采用水下爆炸制造兔ALI模型,其中B、C组分别注射2.5、10×104U/kg乌司他丁注射液。于爆炸前(0h)、爆炸致伤后4、12、24h分别采集静脉血,24h采集支气管肺泡灌洗液(BALF)和部分肺组织标本。ELISA法测定静脉血清及BALF中NF-κB、TNF-α、IL-6的水平。实验结束时测定肺湿干重比(W/D),光镜下观察肺组织病理学改变。结果 水下爆炸致兔急性肺损伤,4h A、B、C组血清NF-κB、TNF-α、IL-6表达较N组升高,差异均有统计学意义(均P<0.05)。经乌司他丁治疗后,B、C组12h时血清NF-κB、TNF-α、IL-6均较A组下降,且B、C组比较,均有统计学差异(均P<0.05)。24h时BALF液NF-κB、TNF-α、IL-6及W/D值,A、B、C组水平均较N组升高(均P<0.05);B、C组均较A组降低,且B、C组比较,均有统计学差异(均P<0.05)。病理检查可见B、C组肺组织出血、水肿及炎细胞浸润较轻,C组效果更好。结论 乌司他丁能减轻水下爆炸所致兔急性肺损伤的肺水肿,其机制为抑制炎症因子NF-κB、TNF-α、IL-6的分泌。

Objective To investigate the effect of ulinastatin（UTI） on acute lung injury induced by underwater explosion in rabbits.Methods Acute lung injury（ALI） was induced by underwater explosion in 40 healthy New Zealand rabbits, and the rabbits were randomly divided into 4 groups with 10 animals in each group： normal control group（N）, model group（A）, low dose UTI group（B） and high dose UTI group（C）. Injection of 2.5, 10 x 104 U/kg UTI was given to group B and C, respectively. Venous blood samples were collected at 0, 4, 12, 24 h after ALI, bronchoalveolar lavage fluid（BALF） and lung tissue samples were collected at 24 h after ALI. The serum and BALF levels of NFk B, TNF-αand IL-6 were measured by ELISA method, and the pathological changes of lung tissue were observed under light microscope.Results The serum levels of NF-k B, TNF-αand IL-6 in groups A, B and C were significantly higher than those in group N 4 h after ALI（P〈0.05）. After treatments with ULT, the NF-k B, TNF-αand IL-6 levels in groups B and C were significantly lower than those in group A at 12 h after ALI（P〈0.05） and there were statistical differences between group B and group C（P〈0.05）. The levels of NF-k B, TNF-α, IL-6 in BALF,and wet/dry weight of lung tissue（W/D） in groups A, B and C were significantly higher than those in group N（P〈0.05） 24 h after ALI; while in groups B and C were lower than those in group A（P〈0.05）. The pathological observation showed that compared to group A the lung tissue hemorrhage, edema and inflammatory cell infiltration were attenuated in treatment-groups, and in group C were milder than those in group B.Conclusion UTI can protect lung tissue from ALI caused by the underwater explosion, which is associated with reducing pulmonary edema and inhibiting inflammatory cytokines secretion.