摘要目的 探讨乌司他丁联合地塞米松对兔爆震伤后急性肺损伤(ALI)的治疗作用.方法 选择健康新四兰大白兔54只中46只制作肺爆震伤ALI模型,其中38只建模成功,8只建模失败.38只按随机数字表法分为损伤组(8只)、治疗Ⅰ组(单纯给予地塞米松,10只),治疗Ⅱ组(单纯给予乌司他丁,10只)和联合治疗组(给予地塞米松+乌司他丁,10只),另8只未受爆震伤动物为对照组.治疗Ⅰ、Ⅱ组和联合治疗组造模成功后0.5,12,24,36,48 h肌肉注射给予相应药物,对照组和损伤组给予等体积等渗盐水.检测伤后即刻及治疗后6,24,48,72 h各组呼吸次数、氧合指数(PaO2/FiO2)及外周静脉血肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、IL-8、中性粒细胞弹性蛋白酶(NE)含量;治疗后72 h处死动物,收集支气管肺泡灌洗液(BALF),检测其中TNF-α、IL-6、IL-8及NE含量,取肺组织测定肺湿/干比重值,并行HE染色观察肺组织病理变化. 结果 各时相点损伤组呼吸次数均较其他各组高,6h时最高(75.0±7.4)次/min,较对照组(33.0±4.5)次/min明显升高(P＜0.01);肺湿/干比重及外周血、BALF中的TNF-α、IL-6、IL-8含量均较对照组明显升高(P＜0.01).损伤组72 h时PaO2/FiO2最低(180.5±12.6) mmHg,较对照组(403.7±8.0) mmHg明显降低(P＜0.01).治疗Ⅰ、Ⅱ组及联合治疗组各指标均有不同程度改善,其中联合治疗组明显优于治疗Ⅰ、Ⅱ组(P＜0.01).与损伤组比较,治疗Ⅰ、Ⅱ组肺组织出血、水肿及炎细胞浸润均较轻,联合治疗组损伤程度最轻;治疗Ⅰ、Ⅱ组比较无明显差异. 结论 乌司他丁联合地塞米松对兔爆震伤所致ALI具有一定治疗作用,且疗效明显优于单用乌司他丁或地塞米松.

abstractsObjective To discuss the therapeutic effect of ulinastatin combined with dexamethasone on blast-induced acute lung injury (ALI) in rabbits.Methods Thirty-eight New Zealand white rabbits with blast-induced ALI were divided into four groups according to the random number table:injury group (n =8),treatment group Ⅰ (dexamethasone alone,n =10),treatment group Ⅱ (ulinastatin alone,n =10),combination therapy group (dexamethasone + ulinastatin,n =10).In addition,8 uninjured rabbits were randomly selected as control group.Treatment groups were given relevant medication by intramuscular injection at 0.5,12,24,36 and 48 hours after successful modeling.Injury group and control group were given equal volume of isotonic saline at the same time.Parameters of respiratory rate,oxygenation index (PaO2/FiO2),TNF-α,IL-6,IL-8 and neutrophil elastase (NE)were detected before and afterfirst treatment at 6,24,48 and 72 hours.All rabbits were sacrificed after 72 hoars to detect TNF-α,IL-6,IL-8 and NE contents in bronchoalveolar lavage fluid (BALF) and to measure wet to dry lung weight ratio.HE staining was performed to observe pathological changes of lung tissues Results In contrast,respiratory rate was high in injury group at each time point,which increased to the peak (75.0 ± 7.4) times/min at 6 hours far higher than (33.0 ± 4.5) times/min in control group (P ＜0.01).Wet to dry lung weight ratio and TNF-α,IL-6 as well as IL-8 contents of the peripheral blood and BAI.F in injury group were significantly higher than those in control group (P ＜0.01).PaO2/ FiO2 in injury group was decreased to the lowest level of (180.5 ± 12.6)mmHg at 72 hours far lower than (403.7-8.0)mmHg in control group (P ＜0.01).While improvements were observed in treatment groups with respect to these indicators,and significantly much better results were detected in combination therapy group rather than in treatment groups Ⅰ and Ⅱ (P ＜ 0.01).Conclusion Ulinastatin combined with dexamethasone is an effective therapy on blast-induced ALI in rabbits,and the effect is significantly better than that with single use of uliinastatin or dexamethasone.