The protective effect of VSL#3 on intestinal permeability in a rat model of alcoholic intestinal injury.
The protective effect of VSL#3 on intestinal permeability in a rat model of alcoholic intestinal injury.
复制标题
DOI：
10.1186/1471-230x-13-151
复制
发表时间：
2013-10-20
影响因子：
2.4
通讯作者：
Wang B
中科院分区：
文献类型：
--
作者：
Chang B;Sang L;Wang Y;Tong J;Zhang D;Wang B
本研究旨在研究益生菌VSL#3在急性酒精性肠损伤中的作用机制，并在大鼠模型中评价VSL#3、谷氨酰胺、VSL#3+谷氨酰胺和热灭活VSL#3治疗的效果。将6至8周龄的雄性野生型大鼠分为7组。为了建立急性酒精性肝病模型，大鼠每12小时接受三个剂量的溶于PBS/40%乙醇的玉米淀粉灌胃给药。给药组在酒精给药前30分钟接受VSLI #3、谷氨酰胺、热灭活VSLI #3或VSLI #3+谷氨酰胺胃内给药。安慰剂组在酒精给药前用PBS处理。通过ELISA和鲎试剂测定血浆中的TNFα和内毒素，并使用电子显微镜、Western印迹和逆转录聚合酶链反应鉴定VSLI #3调节上皮通透性的机制。酒精组内毒素、TNFα明显高于对照组。同时，VSL#3组内毒素和TNFα的表达明显低于乙醇组。随着内毒素和TNFα浓度的升高，上述各组间紧密连接蛋白表达的趋势发生逆转。第二，比较VSL#3+谷氨酰胺、VSL#3+谷氨酰胺和热灭活VSL#3组，我们发现VSL#3和热灭活VSL#3、谷氨酰胺治疗急性酒精性肝病的效果与VSL#3+谷氨酰胺相同，内毒素和TNFα的表达低于酒精组，和紧密连接蛋白的表达高于乙醇组，而VSL#3 +谷氨酰胺组的紧密连接蛋白的表达高于任一药物单独给药组，但无显著差异。我们得出结论，VSLI #3处理可调节肠道微生物群落的生态平衡，防止内毒素和其他细菌产物从肠腔进入门静脉循环，并下调TNFα的表达，否则TNF α可下调紧密连接蛋白的表达并增加上皮通透性。
This study aimed to investigate the mechanism of the probiotic VSL#3 in acute alcoholic intestinal injury, and evaluate the effect of VSL#3, glutamine,VSL#3+glutamine and heat-killed VSL#3 therapy in a rat model. Six- to eight-week-old male wild-type rats were divided into seven groups. To establish the acute alcohol liver disease model, rats received three doses of corn starch dissolved in PBS/40% alcohol administered intra-gastrically every 12 hours. Treatment groups received an intra-gastric dose of VSL#3, Glutamine, heat-killed VSL#3, or VSL#3+Glutamine 30 minutes prior to alcohol administration. The placebo group was treated with PBS prior to alcohol administration. TNFα and endotoxin in plasma was measured by ELISA and Tachypleus Ameboctye Lysate assays, and electron microscopy, Western blotting, and reverse transcription polymerase chain reaction were used to identify the mechanisms of VSL#3 in the regulation of epithelial permeability. First, compared with control group, endotoxin and TNFα in alcohol group was obviously high. At the same time, in VSL#3 group,the expression of endotoxin and TNFα obviously lower than the alcohol group. And the trends of the expression of tight junction proteins in these groups were reversed with the change of endotoxin and TNFα. Second, compared the groups of VSL#3 with glutamine,VSL#3+glutamine and heat-killed VSL#3,we found that both VSL#3 and heat-killed VSL#3, glutamine were as effective as VSL#3+glutamine in the treatment of acute alcohol liver disease, the expression of endotoxin and TNFα were lower than the alcohol group, and tight junction proteins were higher than the alcohol group whereas the expression of tight junction proteins were higher in VSL#3 + glutamine group than either agent alone, but have no significant difference. We conclude that VSL#3 treatment can regulate the ecological balance of the gut microflora, preventing passage of endotoxin and other bacterial products from the gut lumen into the portal circulation and down-regulating the expression of TNFα, which could otherwise down-regulate the expression of tight junction proteins and increase epithelial permeability.