血红素加氧酶-1蛋白转导对脓毒症大鼠急性肺损伤的影响  

Effect of heme oxygenase-1 protein transduction on acute lung injury in septic rats

作　　者：唐隽姣 李青文[1] 何祥虎[1] 王焱林[1] 张宗泽[1] 

机构地区：[1]武汉大学中南医院麻醉科,430071

出　　处：《中华麻醉学杂志》2016年第6期755-757,共3页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81000849）

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210～260g，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0．6mg；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。Objective To evaluate the effect of heme oxygenase-1 （HO-1） protein transduetion 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 long tissues and systemic inflammatory responses.

关 键 词：血红素加氧酶-1 重组融合蛋白质类 转导 遗传 脓毒症 呼吸窘迫综合征 成人 

分 类 号：R459.7[医药卫生—急诊医学]