不同剂量6%HES 130/0.4容量治疗对失血性休克大鼠肺损伤的影响

Effects of volume therapy with different doses of 6% hydroxyethyl starch 130/0.4 on lung injury in a rat model of hemorrhagic shock

目的 评价不同剂量6%羟乙基淀粉130/0.4（6%HES 130/0.4）容量治疗对失血性休克大鼠肺损伤的影响.方法 健康雄性SD大鼠24只,随机分为4组（n=6）,假手术组（S组）、乳酸钠林格氏液组（RS组）和6%HES130/0.4 33ml/kg组（H1组）、6%HES130/0.4 50ml,kg组（H2组）.除S组外,RS组、H1组和H2组均经右颈总动脉放血,制备失血性休克模型.于模型制备成功后RS组静脉输注3倍最大放血量的乳酸钠林格氏液;H1组和H2组分别静脉输注33、50ml/kg 6%HES 130/0.4和乳酸钠林格氏液（总量均为3倍最大放血量）,容量治疗时间45 min.于放血前（T0,基础状态）、容量治疗结束后2 h（T1）、3 h（T2）时采集动脉血样,进行血气分析,计算PaO2/FiO2;最后一次采集血样后,进行支气管肺泡灌洗,测定支气管肺泡灌洗液（BALF）蛋白浓度,取肺组织测定湿,干重比（W/D比值）、TNF-α、m-1β和IL-10的含量,光镜下观察肺组织病理学结果.结果 与S组比较,RS组、H1组和H2组肺组织TNF-α、IL-1β、IL-10含量、BALF蛋白浓度和W/D比值升高,RS组T1.2时PaO2/FiO2降低,H2组T2时PaO2/FiO2降低（P〈0.05）,H1组T1.2时PaO2/FiO2差异无统计学意义（P〉0.05）;与RS组比较,H1组和H2组肺组织TNF-α、IL-1β含量、BALF蛋白浓度和W/D比值降低,H1组T1.2时,H2组T1时PaO2/FiO2升高（P〈0.05）.与H1组比较,H2组T2时PaO2/FiO2降低,肺组织IL-10含量降低（P〈0.05）.H1组和H2组肺组织病理损伤程度轻于RS组,其中H1组病理学损伤程度最轻.结论 6%HES 130/0.4 33和50 ml/kg容量治疗均可减轻失血性休克大鼠肺损伤,33 ml/kg效果更好.

Objective To evaluate the effects of volume therapy with different doses of 6% hydroxyethyl starch 130/0.4 （6% HES 130/0.4） on lung injury in a rat model of hemonhagic shock.Methods Twenty-four male SD rats weighing 220-300 g were randomly divided into 4 groups （ n = 6 each） ： group I sham operation （group S）; group II Ringer＇s solution （group RS）; group HI and IV 2 HES groups （group H1, H2 ）. The animals were anesthetized with intraperitoneal 1% sodium pentobarbital 45 ing/kg. Right common carotid artery （CCA） and left femoral vein were cannulated for blood letting, MAP monitoring, fluid administration and blood sampling. Hemonhagic shock was induced by withdrawing blood from right CCA in group II , III and IV . MAP was reduced to 35-45 mmHg which was maintained for 90 min. In group RS, hemorrhagic shock was resuscitated with Ringer＇s solution 3 times of the volume of blood withdrawn, while group H1 and H2 received HES 33 and 50 ml/kg respectively and Ringer＇ s solution （the total volume was equal to 3 times of the volume of blood removed） . Arterial blood samples were taken before blood letting （T0 , baseline）, and at 2, 3 h after volume therapy （T1,2） for blood gas analysis and PaO2/FiO2 was calculated. The animals were then sacrificed by exsanguination and the lungs were immediately removed for microscopic examination and determination of protein concentration in broncho-alveolar lavage fuid （BALF）, W/D lung weight ratio and TNF-α, IL-1 β and IL-10 contents in the lung.Results TNF-α, IL-1β and IL-10 content in the lung, protein concentration in BALF and W/D ratio were significantly higher in group RS, H1 and H2, while PaO2/FiO2 was significantly lower at T,2 in group RS and at T2 in group H2 than in group S （P 〈 0.05）. TNF-α and IL-1β contents in the lung, protein concentration in BALF and W/D ratio were significantly lower in group H1 and H2 , while PaO2/FiO2 was significantly higher at T,i2 in group H1 and at T1 in group H2 than in group RS （P 〈0.05） . PaO2/FiO2 at T2 and IL-10 content in the lung were significantly lower in group H2 than in group H, （ P 〈 0.05） . The lung damage was significantly ameliorated in group H1 and H2 especially in group H, as compared with group RS. Conclusion Volume therapy with 6% HES 130/0.4 33 or 50 ml/kg can attenuate lung injury in a rat model of hemorrhagic shock and the efficacy of 33 ml/kg is better.