乌司他丁对家兔急性肺损伤保护的实验研究

Protective effects of lung tissue in rabbits with acute lung injury using ulinastatin

目的探讨乌司他丁对急性肺损伤(ALI)家兔肺组织肿瘤坏死因子(TNF-α)mRNA表达的影响及其对肺损伤的治疗作用。方法将30只家兔随机分为对照组(A组),肺损伤对照组(B组)和乌司他丁治疗组(C组),每组10只,B组和C组采用特制多功能撞击机制成急性肺损伤模型,B组经耳缘静脉给予生理盐水静滴,C组经耳缘静脉给予乌司他丁静滴(100 000u/kg),分别在损伤前,损伤后2、4、6h采血测定TNF-α水平,6h后处死动物,取肺组织测定肺水含量、肺体质量比值及观察病理变化、肺组织TNF-α水平、TNF-αmRNA表达。结果与A组相比,B组损伤后肺水含量及肺体质量比值显著增高(P<0.05),镜下见肺间质、肺泡水肿、大量炎细胞浸润。肺组织及血浆TNF-α水平、肺组织TNF-αmRNA表达显著升高(P<0.05),PaO2显著降低(P<0.05),C组经乌司他丁治疗后,与B组比较,肺水含量及肺体质量比值增加少,肺水肿,减轻肺组织及血浆TNF-α水平、肺组织TNF-αmRNA表达降低(P<0.05),PaO2明显升高(P<0.05)。结论乌司他丁能抑制ALI家兔肺组织肺水含量及肺体质量比值增加少,肺水肿,减轻肺组织及血浆TNF-α水平、肺组织TNF-αmRNA表达降低(P<0.05),PaO2明显升高(P<0.05),减轻肺组织的病理损害,治疗ALI。

Objective To study the effects on the expression of the tumor necrosis factor ^（TNF-a）mRNA and its potential functions in rabbits with acute lung injury （ALI） using ulinastatin. Methods Thirty rabbits were randomly divided into three groups：control group（group A） ,ALI control group（group 13） and ulinastatin treatment group（group C） with 10 in each group. ALI model was established by special equipment in group B and group C,and ulinastatin was applied in group C（100 000u/kg）. The levels of TNF-α in plasma were observed at pre-injury and 2,4,6h post-injury. Blood-gas analysis was taken. 6h later, the animals were killed,and the levels of TNF-α in lung tissue, the expression of TNF-α mRNA in lung tissue,content of lung water,lung/body ratio were measured,and pathologic changes of lung tissue were observed microscopically. Results Compared with group A,content of lung water, and lung/body ratio significantly increased （ P〈0.05）, and local hemorrhage, interstitial edema, alveoli exudation, and massive inflammatory cells infiltration were also observed in group B. While the levels of TNF-α in lung tissue and plasma and the expression of TNF-α mRNA in lung tissue significantly increased（P〈0.05） ,PaO2 significantly decreased（P〈0.05）. In group C, compared with that in group B,the content of lung water decreased（P〈0.05） and only mild pathological changes were observed. The levels of TNF-a in lung tissue and plasma and the expression of TNF-a mRNA in lung tissue significantly decrease（P〈0.05）, PaO2 significantly increased（P〈0.05）. Conclusion Ulinastatin could inhibit content of lung water decreased and only mild pathological changes were observed. The levels of TNF a in lung tissue and plasma and the expression of TNF-α mRNA in lung tissue significantly decreased（P〈0.05）, PaO2 significantly increased. Ulinastatin may be effective in treating ALI.