【作者】 杨兴友；

【导师】 张育华；

【作者基本信息】 泸州医学院 ， 中西结合， 2011， 硕士

【摘要】 目的:观察嗜酸乳杆菌对DSS诱导结肠炎大鼠的治疗效果、大鼠结肠黏膜IL-1β和IL-13的表达,探讨嗜酸乳杆菌治疗UC作用机制。方法:采用右旋葡聚糖硫酸钠(DSS)诱导的SD大鼠建立UC模型。SD雄性大鼠42只随机分为正常对照组、嗜酸乳杆菌高浓度组、嗜酸乳杆菌低浓度组、柳氮磺胺吡啶(SASP)、生理盐水(NS)对照组、模型(DSS)对照组共6组,每组7只。正常对照组自由饮水,各实验组自由饮用3%DSS水溶液,2d后改为饮用5%DSS水溶液2d,再恢复为3%DSS水溶液自由饮用,共7d建立大鼠急性UC模型,同时分别给予无菌生理盐水(NS)、嗜酸乳杆菌高剂量(1.0x1011CFU/ml)、嗜酸乳杆菌低剂量(1.0x1010CFU/ml)、SASP(67.5mg/ml)溶液灌胃治疗7d;模型组给予空针插胃。实验期间每日观察大鼠进食、饮水、活动等一般情况,称量体重,观察粪便性状及粪便隐血、便血情况。给药8d后,颈椎脱臼法处死各组大鼠,测量结肠长度,留取各组结肠标本,行HE染色。用免疫组化sp法检测在结肠黏膜上的IL-1β和IL-13表达。结果:1、与DSS模型组、NS组相比,其余各组治疗组大鼠一般情况好。大鼠饮用DSS后,嗜酸乳杆菌两个组、SASP组与DSS组、NS组相比,可降低DAI积分。嗜酸乳杆菌高浓度组结肠长度大于模型对照组,差异有统计学意义(P<0.05);与正常对照组相比无统计学意义(P>0.05)。2、与DSS模型组、NS组相比,嗜酸乳杆菌两个组和SASP组大鼠的结肠组织大体损伤评分和结肠组织病理学改变评分均较低,差异有统计学意义(P<0.05)。3、DSS模型组结肠黏膜IL-lβ含量高于正常组,IL-13含量低于正常组。与DSS模型组和NS组相比,嗜酸乳杆菌两个组和SASP组IL-lβ下降,IL-13呈上升趋势,有显著差异(P<0.01)。嗜酸乳杆菌组和柳氮磺胺吡啶组之间,IL-1β和IL-13的表达均无显著差异性(p>0.05)。结论:1、SS诱导的急性结肠炎能模拟临床UC的发作特点。嗜酸乳杆菌对大鼠急性溃疡性结肠炎有治疗作用。2、嗜酸乳杆菌抑制UC大鼠的炎症反应可能是通过增加IL-13的表达,进而减少IL-1β的产生而实现的。3、嗜酸乳杆菌和SASP对IL-1β和IL-13表达的影响无明显的差异性,说明嗜酸乳杆菌可以取得与抗炎药物相似的疗效。更多还原

【Abstract】 Objective:To investigate the effects of Lactobacillus acidophilus on the expression of IL-1βand IL-13 in colonic mucosa of DSS-induced rats with Ulcerative Colitis(UC) to find its possible mechanism of treating UC.Methods:UC rat were inducsd by dextran sulfate sodium (DSS), 42 healthy male Sprague-Daw1ey rats were randomly divided into 6 groups:normal,lactobacillus treatment(high-dose),lactobacillus treatment(1ow-dose),positive control(SASP),negative control(NS)and model groups,7 rats were involved in each group.The normal group rates were only fed with distilled water. Each experiment group freely drunk 3% DSS, for 2 days,then 3% DSS was changed to 5% DSS to feed for 2 days, last ,3% DSS for 2 days. There were 7 consecutive days and colitis was induced by SD rats.At the same time, every experimental group was orally administratedNS(0.9%),lactobacillus(1.0x1011CFU/ml),lactobacillus(1.0x1010CFU/ml) ,SASP(67.5mg/ml),once a day individually.The body weight and the character of feces as well as occult blood were observed to know disease activity index of every mouse per day.The eight day later,all rats were sacrificed.The colon length was measured and the colony tissue was handled with HE stained.The expression of IL-1βand IL-13 in the colonic mucosa were detected by immunohistochemical staining.Results:1、Compare with DSS-induced rats model group and NS group general the condition of other treatment groups were better)。SD rats induced with DSS solution and Lactobacillus and SASP decreased DAI scores day by day compared with model group and NS group.Compared with model groupthe colon length of lactobacillus treatment(high-dose)group was statistically significant(P<0.05).In compared with normal group,it had no statistical significance(P>0.05).2、Compared with model group and NS group ,gross injury score in colorectal mucosa and histopathological change of lactobacillus group and SASP group were decreased significantly, there were distinguished differences (p<0.05).3、The IL-lβof DSS group colon mucous is higher than the normal group, the IL-13 is lower than the normal group.Compared with model group and NS group,the levels of IL-1βdecreased in lactobacillus treatmentgroup and SASP group,and the levels of IL-13 was increased in these groups(P<0.01). There’s no significant difference between lactobacillus treatment group and SASP group in the levels of IL-1βand the levels of IL-13 in colorectal mucosa of the rats(P>0.05). Conclusion:1、The manifestations of DSS-induced acute colitis rats were similar to clinical symptoms of UC patients. Lactobacillus acidophilus have therapeutical effect to acute UC.2、By increaseing expression of IL-13 and reducing the production of IL-1β,Lactobacillus could control inflammatory response of UC rats .3、There’s no significant difference between lactobacillus treatment groups and SASP group in the levels of IL-1βand the levels of IL-13 in colorectal mucosa of the rats,and there could be a similar results in treating UC between lactobacillus and Anti-inflammatory drugs.更多还原