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研究发现,[药物名称]对瑞士小鼠的小肠和结肠具有有益作用,可对抗 5-氟尿嘧啶的有害作用。

The beneficial effects of on the small intestine and colon of Swiss mice against the deleterious effects of 5-fluorouracil.

机构信息

Postgraduate Program in Pharmaceutical Science, Department of Biophysical and Pharmacology, Federal University of Rio Grande Norte, Natal, Brazil.

Postgraduate Program in Biotechnology /RENORBIO, Department of Biophysical and Pharmacology, Federal University of Rio Grande Norte, Natal, Brazil.

出版信息

Front Immunol. 2022 Oct 21;13:954885. doi: 10.3389/fimmu.2022.954885. eCollection 2022.

Abstract

BACKGROUND

Intestinal mucositis is one of the most common and important side effects of 5-fluorouracil (5-FU). Currently, there are still no specific and effective protocols for its prevention and treatment. The aim of the present study was to evaluate the effect of oral administration of Lacticaseibacillus casei () on the progression of 5-FU-induced intestinal mucositis. Methods: (1x10 CFU/ml) or saline was orally administered to Swiss mice, beginning 15 days before intestinal mucositis induction by single intraperitoneal 5-FU administration (450 mg/kg). Body weight, number of peripheral leukocytes and fecal lactic acid bacteria were monitored. After euthanasia, on day 18, tissue samples from colon and each small intestine segment were collected for histopathology. Jejunal tissues were collected and evaluated for iNOS and TNF-alpha immunoexpression, IL-1-beta, IL-6 and TNF-alpha levels, malonaldehyde (MDA) accumulation, invertase activity and factor nuclear kappa B (NFkB-P65) gene expression, toll like receptor-4 (TLR-4), mucin-2 (MUC-2), occludin and zonula occludens-1 (ZO-1).

RESULTS

The positive impact of on 5-FU-induced leukopenia was observed, but not on 5-FU-induced weight loss in mice. reduced 5-FU-induced inflammation in the colon and small intestine (p<0.05). Decreased TNF-α, IL-1β, IL-6 (p<0.05) and MDA (p<0.05) levels, as well as decreased iNOS and TNF-alpha protein expressions (p<0.05) were found in the jejunum from group. In addition, down-regulated NFKB-P65 (p<0.05) and TLR-4 (p<0.05) gene expressions and up-regulated MUC-2 and mucosal barrier proteins occludin and ZO-1 gene expressions (p<0.05). Furthermore, greater lactic acid bacteria population (p<0.05) was found in the group when compared to control groups.

CONCLUSION

Oral administration can protect the intestine of Swiss mice from 5-FU-induced intestinal mucositis, thus contributing to overall health.

摘要

背景

肠黏膜炎是氟尿嘧啶(5-FU)最常见和最重要的副作用之一。目前,对于其预防和治疗仍没有具体有效的方案。本研究旨在评估口服干酪乳杆菌()对 5-FU 诱导的肠黏膜炎进展的影响。方法:(1x10 CFU/ml)或生理盐水于肠黏膜炎诱导前 15 天开始经腹腔单次给予瑞士小鼠 5-FU(450 mg/kg)。监测体重、外周白细胞计数和粪便中乳酸杆菌数量。安乐死后,在第 18 天收集结肠和各小肠段的组织样本进行组织病理学检查。收集空肠组织,评估诱导型一氧化氮合酶(iNOS)和肿瘤坏死因子-α(TNF-α)免疫表达、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和 TNF-α 水平、丙二醛(MDA)积累、转化酶活性和核因子 kappa B(NFkB-P65)基因表达、Toll 样受体-4(TLR-4)、黏蛋白-2(MUC-2)、闭合蛋白和紧密连接蛋白-1(ZO-1)。结果:观察到干酪乳杆菌对 5-FU 诱导的白细胞减少有积极影响,但对小鼠 5-FU 诱导的体重减轻没有影响。干酪乳杆菌减轻了结肠和小肠的 5-FU 诱导性炎症(p<0.05)。发现组空肠中的 TNF-α、IL-1β、IL-6(p<0.05)和 MDA(p<0.05)水平以及 iNOS 和 TNF-α 蛋白表达降低(p<0.05)。此外,组 NFkB-P65(p<0.05)和 TLR-4(p<0.05)基因表达下调,黏蛋白-2(MUC-2)和黏膜屏障蛋白闭合蛋白和紧密连接蛋白-1(ZO-1)基因表达上调(p<0.05)。此外,与对照组相比,组中乳酸杆菌的数量更多(p<0.05)。结论:口服干酪乳杆菌可保护瑞士小鼠的肠道免受 5-FU 诱导的肠黏膜炎,从而有助于整体健康。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba59/9635922/527e64277b84/fimmu-13-954885-g001.jpg

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