摘要
目的 利用基因工程原理合成携带血红素加氧酶-1（HO-1）基因的乳酸乳球菌，通过对正常大鼠灌胃，观察其对失血性休克大鼠是否有肠黏膜屏障的保护效应，是否能够减少肠道炎症反应的发生。方法 将30只健康清洁级雄性SD大鼠随机分为携带HO-1基因的乳酸乳球菌灌胃组（HO组，n=10）、乳酸乳球菌灌胃组（LL组，n=10）及谷氨酸灌胃组（Glu组，n=10）。Glu组在实验前6h灌胃，其余两组在实验前24h灌胃，复制失血性休克模型。液体复苏后1h取材，比较各组动物的死亡率和平均动脉压（MAP）；采用比色法检测肠组织髓过氧化物酶（MPO）活性；用免疫组化法检测肠组织HO-1、肿瘤坏死因子-α（TNF—α）和白细胞介素-10（IL-10）的灰度值；并行肠组织病理学检查。结果 与LL组和Glu组比较，HO组死亡率明显降低（P均〈0．05）；HO组液体复苏期（5、10、20和30min）MAP均明显升高（P均〈0．05）。与LL组比较，HO组和Glu组的IL-10和HO-1的灰度值均明显增加（P均〈0．05）；与Glu组比较，HO组的HO-1灰度值明显增加（P〈0．05）。3组间TNF—α灰度值比较差异无显著性。LL组、Glu组和HO组肠组织Chiu’S评分分别为（1．93±0．49）分、（1．75±0．58）分和（1．41±0．28）分，HO组与其他两组比较差异均有显著性（P均〈0．05）。结论 携带HO-1基因的乳酸乳球菌灌胃可明显增强失血性休克大鼠HO-1活性，能较好地保护肠黏膜屏障，减轻肠道炎症反应。
Objective To evaluate the effect of gavage of L. lactis recombinant heme oxygenase - 1 （HO - 1） gene on protection of the intestinal mucosa and the inflammation of lower intestine during hemorrhagic shock. Methods A model of hemorrhagic shock was reproduced in 30 SD healthy male rats. They were randomly divided into the L. lactis recombinant HO - 1 gene group （HO group, n= 10）, L. lactis group （LL group, n=10）, and glutamine group （Glu group, n= 10）. Glu was garaged 6 hours and other agents were garaged 24 hours before the experiment. Samples were collected 1 hour after hemorrhagic shock and fluid resuscitation. The mortality, mean arterial pressure （MAP） during hemorrhagic shock and fluid resuscitation, myeloperoxidase （MPO） activity, the pathological changes, and the contents of HO -1, tumor necrosis factor - α （TNF - α） and interleukin - 10 （IL - 10） of the lower intestine were determined immunohistochemically and compared. Results When the results of HO group were compared with Glu and LL groups, the mortality was significantly decreased in the former （both P〈0.05）. In HO group, MAP values at 5, 10, 20 and 30 minutes after fluid resuscitation were significantly elevated （all P〈0. 05）. Compared with LL group, the gray levels＇of IL -10 and HO -1 in HO group and Glu group were significantly increased （all P〈0.05）. Compared with Glu group, the gray level of HO - 1 was significantly increased in HO group （P〈0. 05）. There were no significant differences in the gray levels of TNF-α among three groups. The Chiu＇s grade of HO group [（1.41 ± 0.28） scores was significantly lower than those of LL group and Glu group [（1.93± 0.49） scores and （1.75 ± 0.58） scores, respectively, both P〈0. 053. Conclusion The L. lactis recombinant HO - 1 has the virtue to deliver HO - 1 activity in rats with hemorrhagic shock, which is beneficial for the maintenance of intestinal barrier and anti -inflammation response of the lower intestine.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2007年第4期225-228,I0002,共5页
Chinese Critical Care Medicine
基金
江苏省教育厅开放课题基金资助项目（KJS04002）
