携带IL-10基因的双歧杆菌对溃疡性结肠炎模型小鼠血浆及结肠组织NO和VEGF-A表达影响

Effect of interleukin-10 gene-carrying bifidobacteria on the expression of NO and VEGF-A in the plasma and colon tissue of mice with ulcerative colitis

目的观察携带IL-10基因的双歧杆菌对溃疡性结肠炎(UC)小鼠血浆及结肠组织一氧化氮(NO)与血管内皮生长因子A(VEGF-A)表达的影响,进一步探讨携带IL-10基因的双歧杆菌治疗UC的相关机制。方法筛选出能稳定表达具有生物活性hIL-10蛋白的BL-hIL-10菌株。用5%DSS诱导UC小鼠模型,50只小鼠分为正常对照组、UC模型组、BL治疗组、BL0治疗组和BL-hIL-10治疗组,每组10只。计算小鼠DAI、HE染色评估结肠组织病理学变化;ELISA法测小鼠血浆及结肠组织IL-13、VEGF-A和NO的含量。结果 (1)BL-hIL-10可以降低UC小鼠DAI,减轻UC小鼠结肠组织炎症程度。(2)BL-hIL-10能降低UC小鼠血浆和结肠组织NO、VEGF-A和IL-13水平。结论口服BL-hIL-10对UC小鼠的治疗作用可能与抑制NO产生及下调VEGF-A表达有关。

Objective To explore the effect of interleukin-10gene-carrying bifidobacteria on the expression of nitric oxide（NO）and vascular endothelial growth factor-A（VEGF-A）in the plasma and colon tissue of mice with ulcerative colitis（UC）,and investigate the relevant mechanism of interleukin-10gene-carrying bifidobacteria in the treatment of UC.Methods The BL-hIL-10 bacterial strain capable of expressing bioactive hIL-10 protein steadily was screened.Then 5% dextran sulfate sodium（DSS）was used to induce experimental UC mouse models.50 mice were divided into 5groups randomly：Normal control（NC）group,UC model group,Bifidobacterium treatment（BL）group,Bifidobacterium with empty plasmid treatment（BL0）group and BL-hIL-10 treatment group（n=10）.Disease activity indexes（DAIs）of mice were recorded every day and HE staining of the colon tissue of mice was done for pathological assessment.ELISA was performed to detect the expressions of IL-13,VEGF-A and NO in blood and colon tissue.Results（1）BLhIL-10 reduced the DAI of mice with experimental colitis and relieved the inflammation of colon tissue.（2）BL-hIL-10 reduced the levels of NO,VEGF-A and IL-13 in UC mice.Conclusion Oral administration of BL-hIL-10 can alleviate the inflammation responses of UC in murine models,which may be at least partially due to the inhibition of NO and VEGF-A.