益生菌对活动期溃疡性结肠炎大鼠结肠黏膜组织及IFN-γ、IL-12表达的影响Effect of Probiotic Bacteria on Colonic Mucosa Tissue and the Expression of IFN-γ and IL-12 in Rats with Ulcerative Colitis
王岩;杨立;刘威羽;
WANG Yan;YANG Li;LIU Weiyu;Department of Gastroenterology,People's Hospital of Liaoning Province;
摘要(Abstract):
目的:探讨益生菌VSL#3对三硝基苯磺酸钠(TNBS)诱导的活动期溃疡性结肠炎(UC)大鼠肠道功能及干扰素(IFN)-γ、白介素12(IL-12)表达的影响。方法:21只8周龄SD大鼠,均分为对照组(A组)、TNBS模型组(B组)及VSL#3治疗组(C组),A组给予0.25 m L生理盐水灌肠,B、C组给予100 g/L TNBS 0.25 m L灌肠建立UC大鼠模型;造模第2天A、B组给予生理盐水0.25 m L灌胃,C组给予VSL#3溶液0.25 m L灌胃;第8天时处死大鼠,比较各组大鼠结肠黏膜组织形态、病理学评分、疾病活动指数(DAI)评分、髓过氧化物酶(MPO)活性变化和IFN-γ、IL-12免疫阳性细胞的表达。结果:A组肠组织未见溃疡病灶,B组肠组织可见溃疡,充血水肿程度较重,与B组比较,C组较B组溃疡减少、缩小、并有修复;光镜下A组无明显炎症细胞浸润,B组可见大量中性粒细胞及淋巴细胞浸润,黏膜下急性小血管炎症出血和纤维素样坏死,而C组较B组炎性细胞浸润减少;DAI、病理学评分C组较B组均明显下降(P<0.01),MPO活性低于B组而高于A组(P<0.05);B组IFN-γ和IL-12明显高于A组,C组较B组有降低,但仍明显高于A组(P<0.05);UC模型大鼠肠组织IFN-γ与IL-12的IOD值呈显著正相关(r=0.964 0,P<0.01),UC模型大鼠肠组织IFN-γ、IL-12的IOD值与肠组织病理学评分、MPO活性及DAI呈正相关(r=0.875 0、0.881 0及0.767 1,P<0.05;r=0.837 0、0.850 8及0.713 3,P<0.05)。结论:VSL#3辅助治疗对TNBS诱导的UC大鼠有确切疗效,其作用机制可能与益生菌VSL#3通过有效抑制大鼠结肠黏膜IFN-γ、IL-12的表达有关。
Objective: To investigate the effect of probiotic VSL#3 on function and inflammatory cytokines of rats with active phase of ulcerative colitis induced by TNBS. Methods: Twenty-one adult SD rats were randomly divided into normal control group( group A),TNBS group( group B),VSL#3 treatment group( group C),7 in each group. Group A received enema of 0. 25 m L dose of normal saline while Group B and Group C received enema of 0. 25 m L of TNBS( 100 g / L concentration) to construct UC rats model. After 2 days of model-building,group A and group B received intragastric administration of 0. 25 m L dose of normal saline while group C received intragastric administration of 0. 25 m L dose of VSL#3 solution. At 8thday,rats were killed. Morphologic changes of colonic mucosa tissue,pathology score,MPO activity and expression of IFN-γ,IL-12 immune positive cells were compared between group A,group B and group C. Results: There was no ulcer lesion in colonic mucosa tissue in group A while there was ulcer lesion in colonic mucosa tissue in group B,and the degree of congestion and edema was severe. Compared with group B,ulcer in group C decreased,shrank and repaired itself to some extent. Under light microscope,there existed no obvious inflammatory cell infiltration in group A while in group B there was a lot of infiltration of neutrophile granulocyte and leukomonocyte,and acute inflammation of small blood vessels and fibrinoid necrosis under mucous membrane. Compared with group B,in group C inflammatory cell infiltration decreased,pathology score decreased significantly( P < 0. 01),MPO activity decreased but higher than that of group A( P < 0. 05). IFN-γ and IL-12 expression levels in group B were significantly higher than those of group A while in group C these indexes decreased but still higher than those of group A. There were statistical significance in the differences between group A and group B,between group B and group C,and between group A and group C( P < 0. 05). The IOD value of IFN-γ in UC model rats were positively correlated with IOD value of IL-12( r = 0. 964 0,P < 0. 01). The IOD value of IFN-γ and IOD value of IL-12 in UC model rats were positively correlated with pathology score,MPO activity and DAI( r = 0. 875 0,0. 881 0 and0. 767 1,P < 0. 05; r = 0. 837 0,0. 850 8 and 0. 713 3,P < 0. 05). Conclusion: VSL#3 has adjuvant treatment effects in rats induced by TNBS,whose mechanism may be related to its inhibition of expression of IFN-γand IL-12 in rat colonic mucosa.
关键词(KeyWords):
结肠炎,溃疡性;益生菌VSL#3;干扰素γ;白细胞介素12;基因表达;大鼠,Sprague Dawley
colitis,ulcerative;probiotics VSL#3;interferon-γ;interleukin-12;gene expression;rats,Sprague-Dawley
基金项目(Foundation): 辽宁省自然科学基金项目(201102106)
作者(Authors):
王岩;杨立;刘威羽;
WANG Yan;YANG Li;LIU Weiyu;Department of Gastroenterology,People's Hospital of Liaoning Province;
DOI: 10.19367/j.cnki.1000-2707.2015.11.015
参考文献(References):
- [1]Kellermayer R.Epigenetics and the developmental origins of inflammatory bowel diseases[J].Can J Gastroenterol,2012(12):909-915.
- [2]Morris GP,Beck PL,Herrridge MS,et al.Hapten-induced model of chorinic inflammation and ulceration in the rat colon[J].Gastroenterology,1989(3):795-803.
- [3]Dieleman LA,Palmen MJ,Akol H,et al.Chronic experimental colitis induced by dextran sulphate sodium(DSS)is chatacterized by Th1 and Th2 cytokines[J].Clin Exp Immunol,1998(3):385-391.
- [4]Hamamoto N,Maemura K,Hirata I,et al.Inhibition of dextran sulphate sodium(DSS)-induced colitis in mice by intracolonically administered antibodies against adhesion molecules(endothelial leucocyte adhesion molecule-1(ELAM-1)or intercellular adhension molecule-1(ICAM-1)[J].Clin Exp Immunol,1998(3):462-468.
- [5]Wilson ID,Nicholson JK.The role of gut microbiota in drug response[J].Current pharmaceutical design,2009(13):1519-1523.
- [6]Shen B.Acute and chronic pouchitis-pathogenesis,diagnosis and treatment[J].Nature Reviews Gastroenterology and Hepatology,2012(6):323-333.
- [7]Mc Laughlin SD,Walker AW,Churcher C,et al.The bacteriology of pouchitis:a molecular phylogenetic analysis using 16s rRNA gene cloning and sequencing[J].Annals of Surgery,2010(1):90-98.
- [8]Cain AM,Karpa KD.Clinical utility of probiotics in inflammatory bowel disease[J].Altern Ther Health Med,2011(1):72-79.
- [9]Noor SO,Ridgway K,Scovell L,et al.Ulcerative colitis and irritable bowel patients exhibit distinct abnormalities of the gut microbiota[J].BMC Gastroenterology,2010(1):134.
- [10]江学良,崔慧斐.对我国炎症性肠病诊断治疗规范的共识意见的解析[J].世界华人消化杂志,2008(11):1141-1143.
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- 结肠炎,溃疡性
- 益生菌VSL#3
- 干扰素γ
- 白细胞介素12
- 基因表达
- 大鼠,Sprague Dawley
colitis,ulcerative - probiotics VSL#3
- interferon-γ
- interleukin-12
- gene expression
- rats,Sprague-Dawley