细胞穿透肽PEP-1介导的血红素加氧酶-1对大鼠肠缺血再灌注诱发肝损伤的影响

Effects of heme oxygenase-1 mediated by cell penetrating peptide PEP-1 on liver injury induced by intesti- nal ischemia/reperfusion in rats

目的评价细胞穿透肽PEP-1介导的血红素加氧酶-1（HO-1）对大鼠肠缺血再灌注诱发肝损伤的影响。方法雄性sD大鼠24只，7—9周龄，体重210～260g，采用随机数字表法，将其分为3组（n=8）：假手术组（S组）、肠缺血再灌注组（I／R组）和融合蛋白PEP-1／HO-1组（HO组）。采用夹闭肠系膜上动脉45min，恢复灌注120min的方法制备大鼠肠缺血再灌注模型。HO组于缺血前30min经左侧髂静脉注射融合蛋白PEP-1／HO-10．5mg，S组仅分离闭肠系膜上动脉，但不夹闭。于再灌注120min时，右侧颈总动脉取血样，测定血清AST和ALT的活性；然后处死大鼠，取肝组织，光镜下观察病理学结果，测定MDA含量和SOD活性。结果与s组比较，I／R组和HO组血清AST和AIJT的活性升高，肝组织MDA含量升高，SOD活性降低（P〈0．05）；与I／R组比较，HO组血清AST和ALT的活性降低，肝组织MDA含量降低，SOD活性升高（P〈0．05），肝损伤减轻。结论细胞穿透肽PEP-1介导的HO-1可减轻大鼠肠缺血再灌注诱发的肝损伤。

Objective To evaluate the effects of heme oxygenase-1 （HO-1） mediated by cell penetrating peptide PEP-1 on liver injury induced by intestinal isehemia/reperfusion （I/R） in rats. Methods Twenty-four male Sprague-Dawley rats, aged 7-9 weeks, weighing 210-260 g, were randomly divided into 3 groups （ n = 8 each）： sham operation group （group S）, intestinal I/R group （group I/R） and PEP-1/HO-1 group （group HO）. To establish a model of intestinal I/R, intestines were exteriorized and the superior mesenteric artery was exposed and occluded for 45 min ischemia, and then the clamp was removed for 120 rain reperfusion. The PEP-1/HO-1 fu- sion protein 0.5 mg was injected via ihe left iliac vein 30 min prior to ischemia in group HO. The superior mesen- teric artery was only exposed but not occluded in group S. At the end of reperfusion, blood samples were collected from the right common carotid artery for measurement of serum aspartate aminotransferase （ AST）, alanine aminotransferase （ALT） activities. The rats were then sacrificed and livers were removed for microscopic examination and for determination of malondialdehyde （MDA） content and superoxide dismutase （SOD） activity in liver tissues. Results Compared with group S, serum AST and ALT activities and MDA content in liver tissues were significant- ly increased, while SOD activity in liver tissues was decreased in groups I/R and HO （ P 〈 0.05）. Compared with group I/R, serum AST and ALT activities ~/nd MDA content in liver tissues were significantly decreased, while SOD activity in liver tissues was increased in group HO （P 〈 0.05）. Liver injury induced by intestinal I/R was significantly attenuated in group HO compared with group I/R （P 〈 0.05）. Conclusion HO-1 protein mediated by cell penetrating peptide PEP-1 can attenuate liver injury induced by intestinal I/R in rats.