富硒长双歧杆菌DD98菌株对伊立替康所致小鼠腹泻及肠道菌群的影响

Effect of Selenium-enriched Bifidobacterium longum DD98 on Diarrhea and Intestinal Microflora in Diarrhea Mice Induced by Irinotecan

本研究建立伊立替康所致腹泻小鼠模型,通过长期灌胃富硒DD98(Selenium-enriched Bifidobacterium longum Se-DD98)菌株(一株新的长双歧杆菌菌株),评价其对伊立替康所致腹泻及肠道菌群的影响。正常对照组和伊立替康组小鼠每天灌胃无菌蒸馏水,实验组小鼠每天灌胃低剂量(活菌数1×108CFU/kg)、高剂量(活菌数1×109CFU/kg)Se-DD98菌液,除正常对照组外其他各组在第17 d腹腔注射伊立替康,实验周期为24 d。测定小鼠体重,小鼠腹泻等级,免疫指标,肠道菌群以及回肠组织结构。结果表明:与伊立替康组比较,Se-DD98低、高剂量组小鼠体重显著增加(P<0.05);腹泻等级显著降低(P<0.05);高剂量组白细胞数目显著增加(P<0.05),低、高剂量组脾脏指数和中性粒细胞数目均显著增加(P<0.05),说明Se-DD98具有调节免疫功能的作用。同时,低、高剂量组大肠杆菌、梭菌和拟杆菌含量均比正常组和伊立替康组显著减少(P<0.05),而双歧杆菌含量显著增加(P<0.01)。此外Se-DD98低、高剂量均能减轻伊立替康导致的肠道粘膜、细胞和腺体损伤。上述结果表明Se-DD98可能通过调节肠道菌群和保护肠道粘膜发挥缓解伊立替康导致的腹泻的作用。提示Se-DD98在辅助治疗伊立替康所致的腹泻等方面具有潜在应用前景。

In this research,a irinotecan-induced diarrhea mouse model was established to evaluate the effect of a new Bifidobacterium strain DD98( selenium-enriched Bifidobacterium longum Se-DD98) on diarrhea levels and intestinal microflora.Sterile water or Se-DD98 were orally administered to mice daily for 24 days,irinotecan was injected on day 17,body weight,immune functions,diarrhea levels,intestinal microflora and histologic structure of the ileum were investigated. The results showed that both doses of Se-DD98 significantly increased body weight( P < 0.05),decreased the average levels( P <0.05);high doses of Se-DD98 significantly improved the contents of white blood cells( P < 0.05),both doses increased the levels of spleen index and neutrophils( P < 0.05),which indicate that Se-DD98 can improve the immune function. While Se-DD98 significantly reduced the relative abundance of Bacteroides group,E.coli and Clostridium butyricum( P < 0.05)increased the relative abundance of Bifidobacterium( P < 0.01). Besides,Se-DD98 relieved the damage of intestinal mucosa,intestinal cell damage and glandular reduction induced by irinotecan. So Se-DD98 has potential application in the adjuvant treatment of diarrhea caused by irinotecan.