双歧杆菌对葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎肠道黏膜的保护作用及其对NF-κB的影响

目的随着对炎症性肠病(inflammatory bowel disease,IBD)发病机制的深入研究,肠道微生态与免疫系统的密切关系日益受到重视。本研究旨在评价双歧杆菌单一活菌制剂对葡聚糖硫酸钠(dextran sulfate sodium,DSS)诱导的小鼠结肠炎肠道黏膜的保护作用及其可能作用机制。方法 BALB/c小鼠饮用含7%DSS的饮用水10d,诱导小鼠亚急性结肠炎的模型,模拟人类溃疡性结肠炎。空白对照组(n=6)饮用未添加DSS的饮用水。饮用DSS的小鼠(n=37)随机分为5组,分别给予不同的药物治疗:①提前给予双歧杆菌治疗组(Pre-BIF):在小鼠暴露于DSS前10d及暴露过程中给予双歧杆菌治疗;②强的松治疗组(PRED):在小鼠暴露于DSS同时给予强的松治疗;③双歧杆菌治疗组(BIF):小鼠暴露于DSS的同时给予双歧杆菌治疗;④强的松+双歧杆菌联合治疗组(PRED+BIF):小鼠暴露于DSS的同时给予强的松和双歧杆菌联合治疗;⑤生理盐水对照组(NS):小鼠暴露于DSS的同时给予生理盐水作为对照。不同药物皆以溶液形式灌胃给药。从4方面评价各组的处理反应:①一般情况:包括体重、结肠长度、大体评分;②组织病理评分;③化学比色法检测病变组织髓过氧化物酶(MPO)活性;④免疫组织化学方法检测活化的NF-κB。结果 Pre-BIF治疗组和BIF治疗组的大体评分、组织病理评分、MPO活性与NS对照组相比明显改善(P0.01;P0.05)。Pre-BIF治疗组、BIF治疗组和PRED+BIF治疗组的NF-κB活性评分显著低于NS对照组(P均0.01)。结论双歧杆菌对小鼠DSS结肠炎肠道黏膜具有保护作用,提前应用保护效果更好。双歧杆菌对肠道黏膜的保护作用与抑制NF-κB的活化有关。

The probiotics, Bifidobacterium, ameliorates dextran sulfate sodium induced colitis in mice

Objective There is increasing evidence that the intestinal microflora plays an important role in the pathogenesis of inflammatory bowel disease. In the present study, we investigate the role of probiotics especially bifidobacterium （BIF） in dextran sulfate sodium （DSS）-induced colitis in mice. Furthermore, to in- vestigate the changes of activated nuclear factor-kappa B （NF-κB）. Methods Subacute colitis was induced in BALB/c mice with 7% DSS in their drinking water for 10 days. Controls received normal tap water. Before and during DSS exposure, different medications were given orally as following： （1） Pre-BIF： administration of BIF 10 days before and during DSS exposure; （2） PRED： administration of prednisone during DSS exposure; （3） BIF： administration of BIF during DSS exposure; （4） PRED ＋ BIF： administration both prednisone and BIF during DSS exposure; （5） NS： administration normal saline during DSS exposure. Colitis was quantified by a clinical damage score, body weight, colon length. Inflammatory response was assessed by neutrophil infiltra- tion, determined by histology and myeloperoxidase （MPO） activity. In addition, activation of NF-κB in colon mucosa was further studied by immunohistochemistry. Results Macroscopic score, histological score, MPO activity in Pre-BIF and BIF groups were significantly lower than NS （P 0.01, P 0.05 respectively）. Acti- vated NF-κB score in Pre-BIF, BIF and PRED ＋ BIF were significantly lower than NS （P 0.01）. Conclu- sion Bifidobacterium have protective effect on intestinal mucosa of DSS-induced murine colitis, especially before DSS exposure. Our results therefore suggest that inhibition of NF-κB activation may be involved in the therapeutic and anti-inflammatory effects of Bifidobactrium.