CAJ | 학술논문

目的评价细胞穿透肽PEP-1介导血红素加氧酶-1(HO-1)对大鼠肠缺血再灌注损伤的影响.方法雄性SD大鼠18只,周龄7～9周,体重210～260 g,采用随机数字表法,将大鼠随机分为3组(n=6):假手术组(S组)、肠缺血再灌注组(IR组)和融合蛋白PEP-1/HO-1+肠缺血再灌注组(HO组).采用夹闭肠系膜上动脉45 min,恢复灌注120 min的方法制备大鼠肠缺血再灌注损伤模型.HO组夹闭肠系膜上动脉前30 min,左侧髂静脉注射融合蛋白PEP-1/HO-1 0.5 mg,S组不夹闭肠系膜上动脉,余操作同IR组.于再灌注120 min时处死大鼠取小肠组织,称重后计算肠湿/干重比,测定丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性和HO-1活性,免疫组化法检测肠组织HO-1蛋白的表达,光镜下观察肠组织结构并进行损伤评分.结果与S组比较,IR组和HO组肠湿/干重比和MDA含量升高,SOD活性降低,HO-1活性和蛋白表达水平升高,损伤评分升高(P＜0.05);与IR组比较,HO组肠湿/干重比、MDA含量降低,SOD活性升高,HO-1活性和蛋白表达水平升高,损伤评分降低(P＜0.05).HO组大鼠肠组织病理学损伤较IR组减轻.结论细胞穿透肽PEP-1可将HO-1成功导人大鼠肠组织中的细胞并减轻肠缺血再灌注损伤.
목적 평개세포천투태PEP-1개도혈홍소가양매-1(HO-1)대대서장결혈재관주손상적영향.방법 웅성SD대서18지,주령7～9주,체중210～260 g,채용수궤수자표법,장대서수궤분위3조(n=6):가수술조(S조)、장결혈재관주조(IR조)화융합단백PEP-1/HO-1+장결혈재관주조(HO조).채용협폐장계막상동맥45 min,회복관주120 min적방법제비대서장결혈재관주손상모형.HO조협폐장계막상동맥전30 min,좌측가정맥주사융합단백PEP-1/HO-1 0.5 mg,S조불협폐장계막상동맥,여조작동IR조.우재관주120 min시처사대서취소장조직,칭중후계산장습/간중비,측정병이철(MDA)함량、초양화물기화매(SOD)활성화HO-1활성,면역조화법검측장조직HO-1단백적표체,광경하관찰장조직결구병진행손상평분.결과 여S조비교,IR조화HO조장습/간중비화MDA함량승고,SOD활성강저,HO-1활성화단백표체수평승고,손상평분승고(P＜0.05);여IR조비교,HO조장습/간중비、MDA함량강저,SOD활성승고,HO-1활성화단백표체수평승고,손상평분강저(P＜0.05).HO조대서장조직병이학손상교IR조감경.결론 세포천투태PEP-1가장HO-1성공도인대서장조직중적세포병감경장결혈재관주손상.
Objective To investigate the effects of heme oxygenase-1 (HO-1) mediated by cell penetrating peptide PEP-1 on intestinal ischemia/reperfusion (I/R) injuiy in tats. Methods Eighteen male SD rats aged 7-9 weeks weighing 210-260 g were randomly divided into 3 groups (re = 6 each): sham operation group (group S) , I/R group and PEP-1/HO-1 + I/R group (group HO) . To establish a model of intestinal I/R injury, intestines were exteriorized and the superior mesenteric artery was exposed and occluded for 45 min ischemia, and then the clamp was removed for 120 min reperfusion. The PEP-1/HO-1 fusion protein 0.5 mg was injected via the left iliac vein 30 min prior to ischemia in group HO. The superior mesenteric artery was exposed but not occluded in group S. At the end of reperfusion, the rats were sacrificed and intestinal tissues obtained to determine the intestinal wet/ dry ratio, malondialdehyde (MDA) level, activities of superoxide dismutase (SOD) and HO-1, and HO-1 protein expression. The histological changes in the intestinal mucosa were examined and the injuiy was scored. Results Compared with group S, the intestinal wet/dry ratio, MDA level, HO-1 activity, HO-1 protein expression and injury score were significantly increased, while the SOD activity was significantly decreased in groups I/R and HO ( P ＜ 0.05) . Compared with group I/R, the intestinal wet/dry ratio, MDA level and injury score were significantly decreased, while the SOD activity, HO-1 activity and HO-1 protein expression increased in group HO ( P ＜ 0.05) . The pathologic changes were significantly attenuated in group HO compared with group I/R.Conclusion HO-1 protein can be successfully delivered into intestinal tissues by PEP-1 and has protective effects against intestinal I/R injury.