Han Wei, Mercenier Annick, Ait-Belgnaoui Afifa, Pavan Sonia, Lamine Florence, van Swam Iris I, Kleerebezem Michiel, Salvador-Cartier Christel, Hisbergues Michael, Bueno Lionel, Theodorou Vassilia, Fioramonti Jean
Neurogastroenterology and Nutrition Unit, Institut National de la Recherche Agronomique, Toulouse, France.
Inflamm Bowel Dis. 2006 Nov;12(11):1044-52. doi: 10.1097/01.mib.0000235101.09231.9e.
The use of superoxide dismutases (SODs) in inflammatory diseases is hampered by their short circulatory half-life. To determine whether a bacterial supply of SOD into the colon might improve an experimental colitis, the effects of oral treatment with live recombinant lactic acid bacteria producing different amounts of SOD and those of colonic infusion of SOD were compared. Wistar rats were fitted with a catheter in the proximal colon through which TNBS was administered to induce colitis. Animals received a continuous intracolonic infusion of bovine SOD (40 U per rat per day) for 4 days after TNBS or were treated orally with live recombinant Lactococcus lactis or Lactobacillus plantarum strains (10 colony-forming units (CFU)/d), producing or not producing SOD, for 4 days before and after TNBS. SOD activity of bacterial extracts was 0, 26, 74, and 624 units/10 CFU for L. plantarum, L. lactis, L. lactis SOD, and L. plantarum SOD, respectively. Four days after TNBS, macroscopic and microscopic damage, myeloperoxidase (MPO) activity, and nitrotyrosine immunostaining were evaluated. TNBS induced macroscopic and microscopic damages, an increase in MPO activity, and intense immunostaining for nitrotyrosine. Macroscopic damage and MPO activity were reduced by bovine SOD. These parameters and microscopic damages also were reduced by L. lactis, L. lactis SOD, and L. plantarum SOD, but not by L. plantarum. Nitrotyrosine immunostaining was attenuated after treatment with the 4 bacterial strains. Although not all of the anti-inflammatory effects could be attributed directly to SOD, our results suggest that SOD-producing lactic acid bacteria open a novel approach in inflammatory bowel disease treatment.
超氧化物歧化酶(SOD)在炎症性疾病中的应用受到其循环半衰期短的限制。为了确定向结肠中提供细菌来源的SOD是否能改善实验性结肠炎,比较了口服产生不同量SOD的重组活乳酸菌以及结肠灌注SOD的效果。将导管插入Wistar大鼠的近端结肠,通过导管给予三硝基苯磺酸(TNBS)以诱导结肠炎。在给予TNBS后,动物连续4天接受牛SOD的结肠内灌注(每只大鼠每天40 U),或者在给予TNBS前后4天口服产或不产SOD的重组乳酸乳球菌或植物乳杆菌菌株(10个菌落形成单位(CFU)/天)。植物乳杆菌、乳酸乳球菌、乳酸乳球菌SOD和植物乳杆菌SOD的细菌提取物的SOD活性分别为0、26、74和624单位/10 CFU。给予TNBS 4天后,评估宏观和微观损伤、髓过氧化物酶(MPO)活性以及硝基酪氨酸免疫染色。TNBS诱导了宏观和微观损伤、MPO活性增加以及硝基酪氨酸的强烈免疫染色。牛SOD减轻了宏观损伤和MPO活性。乳酸乳球菌、乳酸乳球菌SOD和植物乳杆菌SOD也减轻了这些参数以及微观损伤,但植物乳杆菌没有。用这4种细菌菌株处理后,硝基酪氨酸免疫染色减弱。尽管并非所有的抗炎作用都可直接归因于SOD,但我们的结果表明,产SOD的乳酸菌为炎症性肠病的治疗开辟了一种新方法。