为探讨热灭活鼠李糖乳杆菌HN001(HK-HN001)对葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导的实验性小鼠结肠炎的保护作用,通过观察结肠长度、疾病活动指数、结肠病理改变、结肠组织氧化应激及促炎因子(IL-1β、IL-6和TNF-α)表达以及结肠通透性、紧密连接蛋白(ZO-1、Claudin-1和E-cadherin)的基因表达,系统研究了HK-HN001(200 mg/kg体质量)对DSS诱导的小鼠结肠炎的保护效果和作用机制。结果显示,HK-HN001对DSS诱导的小鼠结肠炎具有明显的保护效果。其能够有效缓解结肠长度缩短,降低疾病活动指数,减轻结肠组织的水肿、炎性细胞浸润,减轻结肠黏膜损伤,同时降低血清脂多糖水平以及恢复二胺氧化酶活力。进一步研究发现,HK-HN001能够抑制结肠组织的氧化逆境和促炎因子表达,以及调节紧密连接蛋白的转录表达水平。HK-HN001对DSS诱导的小鼠结肠炎有良好的保护作用,HK-HN001具有抗炎性肠病营养食品开发及应用的潜力。
The protective and mechanisms effect of heat-killed Lactobacillus rhamnosus HN001 (HK-HN001) on experimental colitis in mice induced by dextran sodium sulfate (DSS) was investigated. By testing the length, the disease activity index, the pathological changes, the oxidative stress and proinflammatory factors expression, the colonic permeability and the gene expression of tight junction proteins in colon. The results showed that HK-HN001 had a significant protective effect on DSS-induced colitis in mice. HK-HN001 could alleviate the shortening of colon length, the disease activity index, the edema of colon tissue and inflammatory cell infiltration, the damage of colon mucosa, the serum level of lipopolysaccharide and restore the activity of diamine oxidase effectively. HK-HN001 could inhibit the oxidative stress and expression of proinflammatory factors (IL-1β, IL-6 and TNF-α) in colon tissue, and regulate the transcription of tight junction proteins (ZO-1, Claudin-1 and E-cadherin). HK-HN001 had a good protective effect on DSS-induced colitis in mice and the potential to develop an anti-colitis nutrition food.
[1] JEONG S Y,IM Y N,YOUM J Y,et al.L-glutamine attenuates DSS-induced colitis via induction of MAPK phosphatase-1[J].Nutrients,2018,10(3):288.
[2] EICHELE D D,KHARBANDA K K.Dextran sodium sulfate colitis murine model:An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis[J].World Journal of Gastroenterology,2017,23(33):6 016-6 029.
[3] NOVIK G,SAVICH V.Beneficial microbiota.probiotics and pharmaceutical products in functional nutrition and medicine[J].Microbes and Infection,2020,22(1):8-18
[4] ISLAM S U.Clinical uses of probiotics[J].Medicine (Baltimore),2016,95(5):e2 658.
[5] ABRAHAM B P,QUIGLEY E M M.Probiotics in inflammatory bowel disease[J].Gastroenterology Clinics of North America,2017,46(4):769-782.
[6] GANJI-ARJENAKI M,RAFIEIAN-KOPAEI M.Probiotics are a good choice in remission of inflammatory bowel diseases:A meta analysis and systematic review[J].Journal of Cellular Physiology,2018,233(3):2 091-2 103.
[7] MIYAUCHI E,MORITA H,TANABE S.Lactobacillus rhamnosus alleviates intestinal barrier dysfunction in part by increasing expression of zonula occludens-1 and myosin light-chain kinase in vivo[J].Journal of Dairy Science,2009,92(6):2 400-2 408.
[8] BOYLE R J,ROBINS-BROWNE R M,TANG M L K.Probiotic use in clinical practice:What are the risks?[J] The American Journal of Clinical Nutrition,2006,83(6):1 256-1 264.
[9] OHISHI A,TAKAHASHI S,ITO Y,et al.Bifidobacterium septicemia associated with postoperative probiotic therapy in a neonate with omphalocele[J].The Journal of Pediatrics,2010,156(4):679-681.
[10] GOLDENBERG J Z,MA S S Y,SAXTON J D,et al.Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children[J].The Cochrane Database of Systematic Reviews,2013(5):CD006095.
[11] RODRÍGUEZ-NOGALES A,ALGIERI F,VEZZA T,et al.The viability of Lactobacillus fermentum CECT5716 is not essential to exert intestinal anti-inflammatory properties[J].Food & Function,2015,6(4):1 176-1 184.
[12] UENO N,FUJIYA M,SEGAWA S,et al.Heat-killed body of Lactobacillus brevis SBC8803 ameliorates intestinal injury in a murine model of colitis by enhancing the intestinal barrier function[J].Inflammatory Bowel Diseases,2011,17(11):2 235-2 250.
[13] FANG S B,SHIH H Y,HUANG C H,et al.Live and heat-killed Lactobacillus rhamnosus GG upregulate gene expression of pro-inflammatory cytokines in 5-fluorouracil-pretreated Caco-2 cells[J].Supportive Care in Cancer,2014,22(6):1 647-1 654.
[14] LI N,RUSSELL W,DOUGLAS-ESCOBAR M,et al.Live and heat-killed Lactobacillus rhamnosus GG:Effects on proinflammatory and anti-inflammatory cytokines/chemokines in gastrostomy-fed infant rats[J].Pediatric Research,2009,66(2):203-207.
[15] ZHANG L Y,LI N,CAICEDO R,et al.Alive and dead Lactobacillus rhamnosus GG decrease tumor necrosis factor-alpha-induced interleukin-8 production in Caco-2 cells[J].The Journal of Nutrition,2005,135(7):1 752-1 756.
[16] VEZZA T,RODRÍGUEZ-NOGALES A,ALGIERI F,et al.Flavonoids in inflammatory bowel disease:A review[J].Nutrients,2016,8(4):211.
[17] LANDY J,RONDE E,ENGLISH N,et al.Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer[J].World Journal of Gastroenterology,2016,22(11):3 117-3 126.
[18] ADAMS C A.The probiotic paradox:Live and dead cells are biological response modifiers[J].Nutrition Research Reviews,2010,23(1):37-46.
[19] SHEN Z H,ZHU C X,QUAN Y S,et al.Relationship between intestinal microbiota and ulcerative colitis:Mechanisms and clinical application of probiotics and fecal microbiota transplantation[J].World Journal of Gastroenterology,2018,24(1):5-14.
[20] PIQUÉ N,BERLANGA M,MIÑANA-GALBIS D.Health benefits of heat-killed (tyndallized) probiotics:An overview[J].International Journal of Molecular Sciences,2019,20(10):2 534.
[21] LIEVINLE MOAL V,SARRAZIN-DAVILA L E,SERVIN A L.An experimental study and a randomized,double-blind,placebo-controlled clinical trial to evaluate the antisecretory activity of Lactobacillus acidophilus strain LB against nonrotavirus diarrhea[J].Pediatrics,2007,120(4):e795-803.
[22] ZHU L G,HAN J,LI L,et al.Claudin family participates in the pathogenesis of inflammatory bowel diseases and colitis-associated colorectal cancer[J].Frontiers in Immunology,2019,10:1 441.
