摘要目的 评价血红素加氧酶-1(HO-1)蛋白转导对脓毒症大鼠急性肺损伤的影响.方法 健康雄性SD大鼠18只,7～9周龄,体重210～260 g,采用随机数字表法分为3组(n=6):假手术组(Sham组)、脓毒症组(Sep组)和融合蛋白PEP-1-HO-1转导组(HO组).Sep组和HO组采用盲肠结扎穿孔法制备脓毒症模型.HO组于术前1h和术后5h分别经左侧髂静脉注射PEP-1-HO-1融合蛋白0.6 mg;Sham组和Sep组于相应时点给予等容量生理盐水.于术后12h时,右侧颈总动脉采集血样,采用ELISA法测定血清TNF-α和IL-6的浓度;然后处死大鼠取肺组织,光镜下观察病理学结果,测定肺组织湿重/干重(W/D)比值,采用硫代巴比妥酸比色法测定MDA含量.结果 与Sham组比较,Sep组和HO组肺组织W/D比值和MDA含量升高,血清TNF-α和IL-6的浓度升高(P＜0.05),肺组织病理学损伤加重;与Sep组比较,HO组肺组织W/D比值和MDA含量降低,血清TNF-α和IL-6的浓度降低(P＜0.05),肺组织病理学损伤减轻.结论 HO-1蛋白转导可减轻脓毒症大鼠急性肺损伤,其机制可能与抑制肺组织脂质过氧化反应和全身炎性反应有关.

abstractsObjective To evaluate the effect of heme oxygenase-1 (HO-1) protein transduction on acute lung injury in septic rats.Methods Eighteen healthy male Sprague-Dawley rats,aged 7-9 weeks,weighing 210-260 g,were randomly allocated into 3 groups (n =6 each) using a random number table:sham operation group (group Sham),sepsis group (group Sep),and fusion protein PEP-1-HO-1 group (group HO).Sepsis was produced by cecal ligation and puncture (CLP).In group HO,PEP-1-HO-1 fusion protein 0.6 mg was injected via the left iliac vein at 1 h before CLP and 5 h after CLP.The equal volume of normal saline was given instead of PEP-1-HO-1 in Sham and Sep groups.At 12 h after CLP,blood samples were collected from the right common carotid artery for measurement of serum tumor necrosis factoralpha (TNF-α) and interleukin-6 (IL-6) concentrations.The rats were then sacrificed,and lungs were removed for microscopic examination and for determination of wet/dry lung weight ratio (W/D ratio) and malondialdehyde (MDA) content (by thiobarbituric acid colorimetric method).Results Compared with group Sham,the W/D ratio and MDA content were significantly increased,the serum TNF-α and IL-6 concentrations were significantly increased (P＜0.05),and the pathological changes were significantly aggravated in Sep and HO groups.Compared with group Sep,the W/D ratio and MDA content were significantly decreased,the serum TNF-α and IL-6 concentrations were significantly decreased (P＜0.05),and the pathological changes were significantly attenuated in group HO.Conclusion HO-1 protein transduction can attenuate acute lung injury in septic rats,and the mechanism is probably related to inhibition of lipid peroxidation in lung tissues and systemic inflammatory responses.