乌司他丁对大鼠“失血性休克-内毒素”二次打击肺组织水通道蛋白表达的影响

Effect of ulinastatin on aquaporin - 1 （ AQP - 1 ） and aquaporin - 5 （ AQP - 5 ） during hemorrhagic shock complicated with endotoxemia in rats

目的观察乌司他丁对大鼠“失血性休克-内毒素”二次打击肺组织AQP-1和AQP-5表达的影响。方法SD大鼠36只，随机分为三组：假手术对照组（C组）、二次打击组（HS组）、乌司他丁治疗组（UIT组），每组12只。建立“失血性休克-内毒素”二次打击大鼠模型，二次打击30min后UTI组给予静注乌司他丁50kU／kg，HS组给予等容量生理盐水代替。随后两组均回输全部失血及足量林格液进行复苏，复苏后继续观察5h。实验结束前测定肺泡灌洗液蛋白（BALFpro）、肺通透指数（PPI）及肺组织湿／干质量比（W／D）；采用RT—PCR法分别测定肺组织AQP-1和AQP-5mRNA表达；HE染色光镜下观察肺损伤程度。结果与C组比较，HS组及UTI组PPI、BALFpro、W／D等指标均不同程度增高，肺组织AQP-1和AQP-5的表达下调（P〈0．01）；与HS组比较，uTI组PPI、BALFpro、W／D等指标均不同程度降低，AQP-1mRNA和AQP-5mRNA的表达增加（P〈0．01），肺组织损伤程度减轻并显著提高大鼠存活率。结论乌司他丁通过上调AQP-1和AQP-5的表达，有助于减轻失血性休克所致急性肺损伤。

Objective To investigate the effect of ulinastatin on aquaporinl and aquaporin5 in a two - hit model of hemorrhagic shock followed by mimicked infection. Methods Thirty - six SD rats were randomly divided into three groups： control group （C group, surgery, no hemorrhage, and no therapy）, twohit model group （HS group） and ulinastatin therapy group （UTI group）. A two -hit model of hemorrhagic shock complicated with endotoxemia was used. Hemorrhagic shock began with blood withdrawal over 15 min, animals were subjected to massive hemorrhage mean arterial pressure （MAP） = 35 -40 mm Hg for 60 min and followed by intratracheal lipopolysaccharide 1 mg/kg. At 90 min after hemorrhagic shock, a bolus dose of 50 kU/kg ulinastatin was admined to the UTI group, then fluid resuscitation began and last about 60 min, return of all the blood initially shed, plus fluids. After 5hr observation, lung tissue was sampled to measure values of wet -to -dry lung weight ratio（ W/D ） , pulmonary permeability index （PPI）, BALF protein, and reverse transcriptase polymerase chain reaction （ RT - PCR） used for detection the expression of AQP - 1 and AQP - 5. Results Compared with the C group, pulmonary microvascular permeability and W/D were significantly increased in the UTI and HS group, the expression of AQP - 1 and AQP - 5 in lung tissue reduced. Compared with the HS group, pulmonary microvascular permeability and wet - to - dry lung weight ratio were significantly decreased in the UTI group, the UTI maybe attenuated hemorrhagic shock - induced decreased AQP - 1 and AQP - 5 expression in lung tissue. Conclusion These findings showed that ulinastatin can reduce lung tissue damage and pulmonary edema after severe hemorrhagic shock, which caused, in part by up - regulation the expression of AQP - 1 and AQP - 5.