乌司他丁对失血性休克∕复苏大鼠急性肺损伤的影响

Effects of ulinastatin on hemorrhagic shock and resuscitation-induced acute lung injury in rats

目的：评价乌司他丁对失血性休克∕复苏（ HS∕R）大鼠急性肺损伤的影响。方法选择SPF级成年SD大鼠15只，体重300～400 g，2～3月龄，采用随机数字表法，将其分为3组（ n＝5）：假手术组（ S组）、HS∕R组和乌司他丁组（ U组）。HS∕R组和U组通过颈动脉放血建立失血性休克大鼠模型，维持60 min后回输自体血和生理盐水行容量复苏。 U组于容量复苏前静脉注射乌司他丁5万U∕kg（1．0 ml），S组和HS∕R组以等容量生理盐水替代。于颈动脉穿刺置入套管针后（T0）、休克后5 min（ T1）、容量复苏前（ T2）、复苏至预定血压5 min（ T3）、容量复苏后30 min（ T4）、1．5 h（ T5）和2．5 h （ T6）时采集0．5 ml动脉血样，采用ELISA法测定血浆白细胞介素-6（ IL-6）和肿瘤坏死因子-α（ TNF-α）浓度。于T0、T2和T6时采集动脉血样0．5 ml行血气分析，记录pH值、PaCO2、HCO－3和BE值，计算氧合指数（ OI＝PaO2∕FiO2）。于T6时取肺组织行病理学评分，另取肺组织，分离细胞核，采用ELISA法测定核转录因子-κB（ NF-κB） p65水平。结果与S组比较， U组和HS∕R组pH值、HCO－3、BE值和OI降低，PaCO2和血浆IL-6和TNF-α浓度、肺组织NF-κB p65水平、病理学损伤评分升高（ P＜0．05）。与HS∕R组比较，U组血浆IL-6和TNF-α浓度、肺组织NF-κB p65水平、病理学损伤评分降低（ P＜0．05），血气分析指标比较差异无统计学意义（ P＞0．05）。结论乌司他丁虽然可减轻HS∕R大鼠肺损伤，但不足以改善肺氧合功能。

Objective To evaluate the effects of ulinastatin on hemorrhagic shock and resuscitation （ HS∕R）-induced acute lung injury in rats. Methods Fifteen SPF adult Sprague-Dawley rats, aged 2-3 months, weighing 300-400 g, were divided into 3 groups （ n=5 each） using a random number table：sham operation group （ group S ） , HS∕R group and ulinastatin group （ group U ） . Carotid arteries were cannulated for blood pressure monitoring and blood-letting. HS∕R was induced by blood-letting and maintained for 1 h, followed by resuscitation with autologous blood transfusion and infusion of normal saline. After cannulation of carotid arteries （ T0 ） , at 5 min after hemorrhagic shock （ T1 ） , before resuscitation （ T2 ） , at 5 min after the expected blood pressure was achieved following resuscitation （ T3 ） , and at 30 min, 1-5 h and 2-5 h after resuscitation （ T4-6 ） , arterial blood samples were collected for determination of interleukin-6 （ IL-6 ） and tumor necrosis factor-α （ TNF-α） concentrations （ by enzyme-linked immunosorbent assay） . Arterial blood samples were collected at T0 , T2 and T6 for blood gas analysis. The pH value, partial pressure of arterial carbon dioxide （ PaCO2 ） , HCO-3 and base excess （ BE） value were recorded, and oxygenation index （ PaO2∕FiO2 ） was calculated. Lungs were removed at T6 , and pulmonary specimens were obtained for examination of pathological changes which were scored, and nucleus was extracted for determination of nuclear factor-kappa B （ NF-κB ） p65 expression by enzyme-linked immunosorbent assay. Results Compared with group S, the pH values, HCO-3 , BE values and OI were significantly decreased, and PaCO2 , plasma IL-6 and TNF-α concentrations, expression of NF-κB p65 in lung tissues, and pathological scores were increased in U and HS∕R groups. Compared with group HS∕R, the plasma concentrations of IL-6 and TNF-α, expression of NF-κB p65 in lung tissues, and pathological scores were significantly decreased, and no significant changes were found in parameters of blood gas analysis in group U. Conclusion Although ulinastatin can alleviate HS∕R-induced acute lung injury, it is insufficient to improve lung oxygenation in rats.