重组人脑利钠肽对创伤失血性休克导致肺损伤大鼠肺血管通透性的影响

Effects of recombinant human brain natriuretic peptide on vascular permeability of trauma/hemorrhagic shock induced acute lung injury in rats

目的:探讨重组人脑利钠肽(rhBNP)对创伤失血性休克导致急性肺损伤(ALI)大鼠的肺血管通透性的影响。方法:60只SD大鼠随机分为6组:假手术组、模型组、生理盐水组、rhBNP治疗1h组、rhBNP治疗12h组、rhBNP治疗24h组,每组10只大鼠。假手术组完成所有手术操作,但不放血和复苏;模型组完成所有手术操作,放血后给予复苏;生理盐水组在实验前经尾静脉注射无菌生理盐水(2.5ml/kg);rhBNP治疗1、12、24h组大鼠在实验前经尾静脉注射rhBNP(30μg/kg)治疗。各组于术后6h处死大鼠,采集标本,进行肺组织病理学检测及评分,计算肺组织湿/干(W/D)比重、肺水含量,测定肺泡灌洗液(BALF)蛋白含量、髓过氧化物酶(MPO)活性和肺组织匀浆伊文思蓝(EB)含量,并采用酶联免疫吸附测定法(ELISA)测定血清中IL-6和TNF-α水平。结果:肺组织病理学结果显示rhBNP治疗组的肺损伤程度轻于模型组,且rhBNP治疗1、12、24h组肺损伤病理学评分均低于模型组,其中rhBNP治疗12h组和rhBNP治疗24h组评分与模型组比较,差异有统计学意义(P<0.05);rhBNP治疗12h组和rhBNP治疗24h组的BALF蛋白含量、肺W/D比值和肺水含量均明显低于模型组(P<0.05,P<0.01),且rhBNP治疗1、12、24h组的肺匀浆EB含量也明显低于模型组(P<0.05,P<0.01);rhBNP治疗1、12、24h组的肺匀浆MPO活力和血清IL-6、TNF-α水平明显低于模型组(P<0.05,P<0.01)。结论:rhBNP对创伤失血性休克导致的ALI有保护作用,可能是通过降低ALI时肺血管通透性来实现的。

Objective：To investigate the effects of recombinant human brain natriuretic peptide（rhBNP）on vascular permeability of trauma/hemorrhagic shock induced acute lung injury in rats.Method：Sixty SD rats were randomly divided into six groups including sham operation group,model group,saline group,rhBNP treatment 1h group,rhBNP treatment 12 hgroup and rhBNP treatment 24 hgroup.There were 10 rats in each group.All operations except bleeding and resuscitation were done in sham operation group.All steps in operation were done in model group.Sterile saline（2.5ml/kg）were injected before the experiment though tail vein in saline group rats.Similarly,rhBNP（30μg/kg）were used before the experiment though tail vein of rats in rhBNP treatment 1、12、24h group.Rats were killed 6hours after the operation,meanwhile specimens were obtained.Then alveolar lavage fluid（BALF）protein content,lung wet/dry（W/D）weight and lung water content were calculated.Myeloperoxidase（MPO）activity,evans blue（EB）contentin lung tissue homogenate,levels of IL-6and TNF-αwere also detected.Eventually,pathology detection and scoring were done.Result：The results of pathology and scoring showed that lung injuries in rhBNP treatment 1、12、24hgroup were less than that in model group,and lung injury pathology scoring in rhBNP treatment 12、24hgroup were significantly lower than that in the model group（P〈0.05）.BALF protein content,lung W/D weight ratio and lung water content in rhBNP treatment 12、24hgroup were significantly reduced than those in model group（P〈0.05,P〈0.01）.Moreover,EB contentin lung tissue homogenate was also decreased in rhBNP treatment 1、12、24hgroup（P〈0.05,P〈0.01）.Similarly,MPO activity and levels of IL-6and TNF-αin rhBNP treatment 1、12、24hgroup were lower than those in model group（P〈0.05,P〈0.01）.Conclusion：Pretreatment of recombinant human brain natriuretic peptideshows the beneficial effect on acute lung injury induced by trauma/hemorrhagic shock in rats.The decrease of pulmonary vascular permeability may be involved in the mechanism of actions of recombinant human brain natriuretic peptid effects.