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嗜热链球菌 TH-4 对化疗药物 5-氟尿嘧啶(5-FU)诱导的肠道黏膜炎的影响。

Effects of Streptococcus thermophilus TH-4 on intestinal mucositis induced by the chemotherapeutic agent 5-Fluorouracil (5-FU).

机构信息

Centre for Paediatric and Adolescent Gastroenterology, Department of Microbiology, Children, Youth and Women’s Health Service, North Adelaide, South Australia.

出版信息

Cancer Biol Ther. 2009 Mar 15;8(6):505-11.

Abstract

Beneficial bacteria (probiotics) and probiotic-derived factors have the potential to ameliorate disorders of the intestine. The aim of this study was to compare live Streptococcus thermophilus TH-4 (TH-4), dead TH-4 and TH-4 supernatant in rats treated with 5-Fluorouracil. Rats were randomly allocated to five treatment groups (n = 8–10): Saline + Water; 5-FU + Skim Milk; 5-FU+ Live TH-4; 5-FU + Supernatant TH-4; and 5-FU + Dead TH-4.5-FU (150 mg.kg-1) was administered by a single intraperitoneal injection on day zero; animals were killed on day four. Treatments were administered daily from days -2 to +3 via oro-gastric gavage. Metabolic parameters were measured daily. Blood was obtained by cardiac puncture, and intestinal tissues removed for quantitative and qualitative histological assessment, including: villus height and area; crypt depth and area, mitotic count and crypt fission;biochemical determination of sucrase and myeloperoxidase (MPO)activity; and disease severity scoring. One-way ANOVA statistical analyses were conducted for the majority of outcome measures. Live TH-4 significantly reduced disease severity score by 13% (p< 0.05), and partially normalized mitotic counts compared with 5-FU + Skim Milk controls. Live and Supernatant TH-4 reduced crypt fission by 69% and 48% (p < 0.05), respectively, compared to 5-FU + Skim Milk controls. No significant differences (p > 0.05) in the occurrence of bacteraemia were evident across all groups. Live TH-4 partially normalized mitotic count and histological severity score in 5-FU treated rats. The inhibitory effect of live TH-4 and TH-4 Supernatant on crypt fission suggests therapeutic utility in the prevention of disorders characterized by increased crypt fission,such as colorectal carcinoma.

摘要

有益细菌(益生菌)和益生菌衍生因子有可能改善肠道紊乱。本研究旨在比较 5-氟尿嘧啶处理大鼠中活菌嗜热链球菌 TH-4(TH-4)、死菌 TH-4 和 TH-4 上清液的作用。大鼠随机分为五组(n=8-10):生理盐水+水;5-FU+脱脂奶;5-FU+活菌 TH-4;5-FU+TH-4 上清液;5-FU+死菌 TH-4。第 0 天经腹腔单次注射 5-FU(150mg/kg);第 4 天处死动物。从第-2 天到第+3 天每天经口灌胃给药。每天测量代谢参数。经心脏穿刺取血,取肠组织进行定量和定性组织学评估,包括:绒毛高度和面积;隐窝深度和面积、有丝分裂计数和隐窝分裂;蔗糖酶和髓过氧化物酶(MPO)活性的生化测定;以及疾病严重程度评分。对大多数结果指标进行单因素方差分析统计。与 5-FU+脱脂奶对照组相比,活菌 TH-4 使疾病严重程度评分降低了 13%(p<0.05),有丝分裂计数部分恢复正常。活菌和上清液 TH-4 使隐窝分裂分别降低了 69%和 48%(p<0.05),与 5-FU+脱脂奶对照组相比。所有组之间的菌血症发生率均无显著差异(p>0.05)。活菌 TH-4 使 5-FU 处理大鼠的有丝分裂计数和组织学严重程度评分部分恢复正常。活菌 TH-4 和 TH-4 上清液对隐窝分裂的抑制作用表明,其在预防以隐窝分裂增加为特征的疾病方面具有治疗作用,如结直肠癌。

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