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双歧三联活菌胶囊对于实验性结肠炎小鼠肠及肝脏IL-6表达的影响

发布时间:2018-05-17 01:42

  本文选题:溃疡性结肠炎 + 肝脏病变 ; 参考:《山西医科大学》2017年硕士论文


【摘要】:溃疡性结肠炎(ulcerative colitis,UC)是一种病因未明的慢性、反复发作的炎症性肠病(inflammatory bowel disease,IBD),在世界范围内,UC的发病率呈逐年升高的趋势,目前认为UC与感染、环境、黏膜免疫功能以及机体的遗传易感性、肠道微生态等多种因素有关。虽然UC的病变主要累及肠道,但各种形式的肠外表现在UC的临床表现里也尤为突出,肝脏病变肝脏病变即是UC最常出现的肠外病变之一。目前研究推测UC时,肠黏膜屏障的损伤使得肠粘膜的通透性增加,进而使得肠道菌群通过受损的肠黏膜移位进入血流,引起门静脉菌血症,并累及肝脏,使肝脏Kupffer细胞激活,并促进Kupffer细胞生成细胞因子(如IL-6等),进而引发炎症的瀑布反应,损伤肝细胞,阻碍肝细胞的分泌、代谢等功能,引起肝脏病变、肝细胞损坏,导致肝胆疾病的发生。双歧三联活菌胶囊是一类联合的菌群,是由乳酸杆菌、双歧杆菌及粪肠球菌三者合理配比制成的,口服双歧三联活菌胶囊后进入肠道可补充肠道的生理性细菌,并通过生理性菌群的大量繁殖,可抑制其他有害微生物的生长,并发挥其生物屏障的作用,使得肠道粘膜的通透性降低,并防止细菌移位,减少内毒素的吸收和产生,从而减少释放的炎症因子的量,并进一步使得肝功能好转。本实验初步探讨双歧三联活菌胶囊对于实验性结肠炎小鼠肠及肝脏的IL-6表达的影响,本实验将45只BALB/c小鼠随机分为3组,分别为正常组、DSS组、DSS+双歧三联活菌胶囊治疗组。10d后处死小鼠,去眼球取血,并取小鼠的结肠和肝脏组织,测量小鼠结肠的长度,观察各组小鼠肠及肝脏的大体形态和组织病理学改变,并用ELISA方法检测小鼠结肠及肝脏组织IL-6的变化。实验结果显示通过对实验性结肠炎小鼠用双歧三联杆菌胶囊进行治疗,DSS组小鼠的DAI评分、病理组织学评估、ELISA方法测得的小鼠结肠及肝脏组织IL-6的水平均较正常组明显升高(P0.05)。同时DSS+双歧三联活菌胶囊组小鼠的DAI评分、病理组织学评估、ELISA方法测得的小鼠结肠及肝脏组织IL-6的水平均较DSS组显著降低(P0.05)。本实验研究证实双歧三联活菌胶囊对于DSS诱导的小鼠实验性结肠炎及肝脏病变具有治疗的作用,进一步证实了双歧三联活菌胶囊可以调节肠道的菌群,修复肠黏膜屏障,降低肠道粘膜的通透性,从而防止细菌移位,减少内毒素的产生和吸收,改善肠道与肝脏的功能,本实验也表明双歧三联活菌胶囊可下调炎症因子的表达,减轻肠黏膜及肝脏炎症反应,有利于UC及其伴发的肠外表现的综合治疗,为临床治疗UC相关肝胆病变提供新的诊疗思路。
[Abstract]:Ulcerative colitis (UC) is a chronic, recurrent and recurrent inflammatory bowel disease (inflammatory bowel disease, IBD). In the world, the incidence of UC is increasing year by year. At present, it is considered that UC and infection, environment, mucosal immune function, genetic susceptibility to the body, intestinal microecology, etc. Although the lesions of UC are mainly involved in the intestinal tract, all forms of extraintestinal manifestations are particularly prominent in the clinical manifestations of UC. Liver pathological changes are one of the most common extraintestinal lesions that occur in UC. At present, the damage of the intestinal mucosal barrier increases the permeability of the intestinal mucosa when UC is conjectured, and the intestinal microflora may be affected by the intestinal microflora. The damaged intestinal mucosa translocation into the blood flow, cause the portal venous bacteremia, and involve the liver, activate the liver Kupffer cells, and promote the Kupffer cells to produce cytokines (such as IL-6, etc.), and then cause the waterfall reaction of the inflammation, the damage of the liver cells, the secretion of liver cells, the metabolism of liver cells, the damage of liver cells and the hepatobiliary disease. The Bifidobacterium capsule is a combined group of bacteria, which is made up of three groups of Lactobacillus, Bifidobacterium and Enterococcus faecalis. The oral Bifidobacterium capsule enters the intestine to supplement the physiological bacteria in the intestines, and can inhibit the growth of other harmful microorganisms through the large reproduction of the physiological bacteria. The effect of the biological barrier can reduce the permeability of the intestinal mucosa, prevent the bacterial translocation, reduce the absorption and production of endotoxin, reduce the amount of the inflammatory factors released, and further improve the liver function. The IL-6 expression of the Bifidobacterium bifidus Capsule on the intestines and liver of experimental colitis mice was preliminarily discussed. In this experiment, 45 BALB/c mice were randomly divided into 3 groups: normal group, DSS group, DSS+ Bifidobacterium Bifidobacterium capsule treatment group, after.10d, the mice were killed, blood was removed from the eyeball, and the colonic and liver tissues of mice were taken to measure the length of the colon, and the general morphology and histopathological changes of the intestines and liver in each group were observed, and ELI was observed. SA method was used to detect the changes of IL-6 in the colon and liver tissue of mice. The experimental results showed that the DAI score of the DSS group and the histopathological evaluation of the mice in the experimental colitis were evaluated, and the level of IL-6 in the colon and liver tissues of the mice was significantly higher than that in the normal group (P0.05), and DSS+ was observed by ELISA method (P0.05). The DAI score of mice in the Bifidobacterium capsule group was evaluated by histopathology. The level of IL-6 in the colon and liver tissues of mice measured by ELISA was significantly lower than that of the DSS group (P0.05). This experimental study confirmed the effect of Bifidobacterium Capsule on the experimental colitis and liver disease induced by DSS in mice, and further confirmed the effect. The Bifidobacterium capsule can regulate the intestinal flora, repair intestinal mucosal barrier, reduce the permeability of intestinal mucosa, prevent bacterial translocation, reduce the production and absorption of endotoxin, and improve the function of intestinal and liver. This experiment also shows that Bifidobacterium capsule can reduce the expression of inflammatory factors and reduce intestinal mucosa and liver inflammation. The disease response is beneficial to the comprehensive treatment of UC and its extra intestinal manifestations, and provides a new way of thinking for clinical treatment of UC related liver and gallbladder diseases.
【学位授予单位】:山西医科大学
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R574.62

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