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VSL#3 可预防小鼠溃疡性结肠炎相关癌变。

VSL#3 can prevent ulcerative colitis-associated carcinogenesis in mice.

机构信息

Department of Gastroenterology, PUMC Hospital, CAMS and PUMC, Beijing 100730, China.

National Cancer Center/Cancer Hospital, CAMS and PUMC, Beijing 100021, China.

出版信息

World J Gastroenterol. 2018 Oct 7;24(37):4254-4262. doi: 10.3748/wjg.v24.i37.4254.

Abstract

AIM

To investigate the effects of VSL#3 on tumor formation, and fecal and intestinal mucosal microbiota in azoxymethane/dextran sulfate sodium (AOM/DSS) induced mice model.

METHODS

C57BL/6 mice were administered AOM/DSS to develop the ulcerative colitis (UC) carcinogenesis model. Mice were treated with 5-ASA (75 mg/kg/d), VSL#3 (1.5 × 10 CFU/d), or 5-ASA combined with VSL#3 by gavage from the day of AOM injection for three months (five days/week). The tumor load was compared in each group, and tumor necrosis factor (TNF-α) and interleukin (IL)-6 levels were evaluated in colon tissue. The stool and intestinal mucosa samples were collected to analyze the differences in the intestinal microbiota by 16s rDNA sequencing method.

RESULTS

VSL#3 significantly reduced the tumor load in AOM/DSS-induced mice model and decreased the level of TNF-α and IL-6 in colon tissue. The model group had a lower level of and higher level of and in fecal microbiota than the control group. After the intervention with 5-ASA and VSL#3, and were increased, while and were reduced. 5-ASA combined with VSL#3 increased the and decreased the . The intestinal mucosal microbiota analysis showed a lower level of and _UCG-014 and higher level of in the model group as compared to the control group. After supplementation with VSL#3, was increased. 5-ASA combined with VSL#3 increased the level of both and .

CONCLUSION

VSL#3 can prevent UC-associated carcinogenesis in mice, reduce the colonic mucosal inflammation levels, and rebalance the fecal and mucosal intestinal microbiota.

摘要

目的

研究 VSL#3 对氧化偶氮甲烷/葡聚糖硫酸钠(AOM/DSS)诱导的小鼠模型中肿瘤形成、粪便和肠道黏膜微生物群的影响。

方法

给予 C57BL/6 小鼠 AOM/DSS 以建立溃疡性结肠炎(UC)癌变模型。从 AOM 注射之日起,通过灌胃用 5-ASA(75mg/kg/d)、VSL#3(1.5×10 CFU/d)或 5-ASA 联合 VSL#3 对小鼠进行为期三个月(每周 5 天)的治疗。比较各组的肿瘤负荷,并评估结肠组织中肿瘤坏死因子(TNF-α)和白细胞介素(IL)-6 的水平。通过 16s rDNA 测序方法收集粪便和肠道黏膜样本,分析肠道微生物群的差异。

结果

VSL#3 可显著降低 AOM/DSS 诱导的小鼠模型中的肿瘤负荷,并降低结肠组织中 TNF-α和 IL-6 的水平。模型组粪便微生物群中的 和 水平低于对照组,而 和 水平高于对照组。用 5-ASA 和 VSL#3 干预后, 和 增加,而 和 减少。5-ASA 联合 VSL#3 增加了 ,减少了 。肠道黏膜微生物群分析显示,模型组 和 _UCG-014 的水平低于对照组,而 的水平高于对照组。补充 VSL#3 后, 增加。5-ASA 联合 VSL#3 增加了 和 的水平。

结论

VSL#3 可预防小鼠的 UC 相关癌变,降低结肠黏膜炎症水平,并使粪便和黏膜肠道微生物群再平衡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f9/6175759/01fa710c679b/WJG-24-4254-g001.jpg

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