摘要目的 探讨血红素加氧酶-1(HO-1)蛋白转导对脓毒症大鼠肠损伤的影响.方法 健康雄性SD大鼠24只,年龄7～9周,体重210 ～ 260 g,采用随机数字表法分为4组(n=6):假手术组(S组)、脓毒症组(CLP组)、低剂量PEP-1-HO-1融合蛋白+CLP组(P1组)和高剂量PEP-1-HO-1融合蛋白+ CLP组(P2组).采用盲肠结扎穿孔(CLP)法制备大鼠脓毒症模型.于CLP前1h和CLP后5h,P1组和P2组分别静脉注射PEP-1-HO-1融合蛋白0.3和0.6 mg.于CLP后12 h,取动脉血样,测定血清TNF-α和IL-6浓度,随后处死大鼠,取肠组织,光镜下观察肠组织病理学结果,测定丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性.结果 与S组比较,CLP组、P1组和P2组血清TNF-α、IL-6浓度和肠组织MDA含量升高,SOD活性降低(P＜0.05);与CLP组比较,P1组和P2组血清TNF-α、IL-6浓度和肠组织MDA含量降低,SOD活性升高(P＜0.05);与P1组比较,P2组血清TNF-α、IL-6浓度和肠组织MDA含量降低,SOD活性升高(P＜0.05).P1组和P2组肠组织病理学损伤较CLP组减轻.结论 HO-1蛋白转导可减轻脓毒症大鼠肠损伤,机制与抑制全身炎性反应和肠组织脂质过氧化反应有关.

abstractsObjective To investigate the effects of heme oxygenase-1 (HO-1) protein transduction mediated by cell penetrating peptide PEP-1 on intestinal injury in a rat model of sepsis induced by cecal ligation and puncture (CLP).Methods Twenty-four healthy male Sprague-Dawley rats,aged 7-9 weeks,weighing 210-260 g,were randomly divided into 4 groups (n =6 each) using a random number table:sham operation group (group S),group CLP,low-dose fusion protein PEP-1-HO-1 + CLP group (group P1) and high-dose fusion protein PEP-1-HO-1 + CLP group (group P2).Fusion protein PEP-1-HO-1 0.3 mg was administrated via the left iliac vein at 1 h before CLP and 5 h after CLP in group P1.Fusion protein PEP-1-HO-1 0.6 mg was administrated via the left iliac vein at 1 h before CLP and 5 h after CLP in group P2.The equal volume of normal saline was given instead of PEP-1-HO-1 in the other groups.The animals underwent laparotomy,but the caecum was not ligated or punctured in group S.Blood samples were collected at 12 h after CLP from the right common carotid artery for measurement of serum TNF-α and IL-6 levels.The rats were then sacrificed and intestines were removed for microscopic examination and for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in intestinal tissues.Results Compared with group S,the serum TNF-α and IL-6 levels,and MDA content in intestinal tissues were significantly increased,while SOD activity in intestinal tissues was decreased in CLP,P1 and P2 groups.Compared with group CLP,the serum TNF-α and IL-6 levels,and MDA content in intestinal were significantly decreased,while SOD activity in intestinal tissues was increased in P1 and P2 groups.Compared with group P1,the serum TNF-α and IL-6 levels,and MDA content in intestinal tissues were significantly decreased,while SOD activity in intestinal tissues was increased in group P2.The pathological changes of intestines were significantly mitigated in P1 and P2 groups as compared with group CLP.Conclusion HO-1 protein transduction attenuates intestinal injury induced by sepsis in rats,and the mechanism is related to inhibition of systemic inflammatory responses and lipid peroxidation in intestinal tissues.