植物乳杆菌对白细胞介素-10基因敲除小鼠结肠炎的治疗作用  

The effect of Lactobacillus plantarum on the treatment of colitis in interleukin-10 knockout mice

作　　者：叶胜青[1] 丁在咸[2] 张旻[3] 陈红旗[2] 杭晓敏[3] 秦环龙[2] 

机构地区：[1]江苏大学附属江滨医院普外科,江苏省镇江市212001 [2]上海交通大学附属第六人民医院普外科 [3]上海交通大学大昂立医药研究院

出　　处：《中华消化杂志》2011年第9期619-624,共6页Chinese Journal of Digestion

摘　　要：目的评估植物乳杆菌（Lactobacillus plantarum，Lp）对白细胞介素-10基因敲除（interleukin-10 knockout，IL-10^-/-）小鼠结肠炎的治疗作用，并探讨其可能的作用机制。方法8周龄雌性IL-10^-/-小鼠和WT小鼠各20只。各自平均分成2组，即WT组、WT＋Lp组、IL-10^-/-组和IL-10^-/-＋LP组。WT和IL-10^-/-组予0．5ml PBS灌胃，WT＋Lp和IL-10^-/-＋Lp组予0．02g Lp（0．5ml）灌胃，每天摄入Lp1×10^9菌落形成单位（CFU），持续灌胃4周后实验结束。实验开始前（0周）及开始后每隔1周收集小鼠新鲜粪便1次，直至实验结束。实验结束后将小鼠处死，记录各组小鼠体重变化，并测量其结肠长度和湿重，切取新鲜结肠组织标本做病理切片及结肠黏膜促炎因子肿瘤坏死因子（TNF）-α和干扰素-γ（IFN-γ）检测。并对小鼠新鲜粪便作选择性细菌培养，观察Lp在正常小鼠和炎症小鼠体内的定植情况及其对肠道菌群的调节作用。结果与WT小鼠相比，IL-10^-/-小鼠腹泻较重，体重亦明显下降（P〈0．05），存在严重营养不良，而经Lp治疗后IL-10^-/-小鼠腹泻得到缓解，体重亦明显增加（P〈0．05）。病理学检查显示，所有IL-10^-/-小鼠皆发生肠道炎症，经Lp治疗后肠道炎症得到明显改善，黏膜溃疡、上皮增生及黏膜固有层淋巴细胞和中性粒细胞浸润明显减轻，病理学评分明显降低（P〈0．01）。IL-10^-/-小鼠经Lp治疗后结肠湿重及湿重与长度比出现明显变化（P〈0．01），结肠水肿和增厚现象得到明显改善。IL-10^-/-组小鼠结肠TNF—α和IFN—γ含量分别为（377．4±84．4）μg／g和（602．6±108．1）μg／g，均较WT组明显增加[（139．2±32．7）μg／g和（173．o±52．4）μg／g，P〈0．05）]。Lp干预4周后，IL-10^-/-＋Lp组小鼠结肠TNF-α和IFN—γ的含量分别为（207．2±65．7）μg／g和（442．1±138．4）μg／g，均较IL-10^-/-组显著降低（P〈20Objective To evaluate the role of Lactobacillus plantarum （LP） in the treatment of colitis in interleukin （IL）-10 knockout （IL-10） mice and to explore its possible mechanisms. Methods Eight weeks old female wildtype （WT） mice and IL-10^-/- mice, twenty mice of each type, were randomly assigned to four groups, WT group, WT＋ LP group, IL-10^-/-group and IL-10^-/- LP group. The WT and IL-10^-/- mice were garaged with 0. 5 ml saline, WT＋Lp and IL IL-10^-/- ＋Lp groups were garaged with Lp 0. 02 g （0.5 ml）, took Lp 1 × 10^9 cfu everyday, continued for 4 weeks and then the experiment finished. The fresh mice faeces was collected once every week before （week 0） and during the experiment. The mice were executed at the end of experiments, the change of mice weight Was recorded, the length and the wet weight of colon were measured, fresh colon tissue specimens were taken for biological slices and proinflammatory cytokines TNF-α and IFN-γ were measured in colon mucosa. The fresh faeces were selectively cultured. The colonization of Lp in normal and colitis mice and its regulation role in intestinal flora were observed. Results Compared with WT mice, IL-10^-/- mice demonstrated severe diarrhea, significantly decreased in body weight （P 〈0.05）and serious malnutrition. After Lp treatment, diarrhea relieved in IL-10^-/- mice and the body weight increased significantly （P〈0.05）. Pathological examination suggested that 100 % of IL-10^-/- mice had intestinal inflammation, however after Lp treatment intestinal inflammation improved significantly. Mucosal ulcer, epithelial hyperplasia, the infiltration of neutrophils and lymphocytes in the lamina propria were also significantly reduced. The histopathological score was significantly lowered （P〈0.01）. After Lp treatment, colon wet weight and the ratio of wet weight to length of IL- 10^-/- mice changed significantly （P〈0.01）. Colon edema and thickening improved remarkably. The TNF-α and IFN-γ concentration of colon in IL-10^-/-

关 键 词：益生菌 乳杆菌属 结肠炎 白细胞介素-10 小鼠 基因敲除 

分 类 号：R285.5[医药卫生—中药学]