肠道菌群失调作为始发因素参与腹泻型肠易激综合征的发生与发展分析

Analysis of intestinal flora imbalance as an initial factor in the occurrence and development of diarrhea⁃predominant irritable bowel syndrome

目的探究肠道菌群在腹泻型肠易激综合征(IBS‑D)发生中的作用。方法将经过肠内抗生素清扫的小鼠随机分为实验组和对照组,分别给予实验组和对照组小鼠IBS‑D粪便和正常小鼠粪便进行粪菌移植实验。观察2组小鼠粪便含水量、肠道传输时间、肠道敏感性等指标。通过实时荧光定量PCR(qRT‑PCR)检测结肠组织中核因子κB(NF‑κB)、Toll样受体4(TLR4)、髓样分化因子88(MyD88)、白细胞介素‑1β(IL‑1β)、白细胞介素‑6(IL‑6)、肿瘤坏死因子α(TNF‑α)的mRNA表达情况,采用蛋白质印迹法检测上述蛋白的表达情况。结果与对照组小鼠相比,移植IBS‑D粪便的实验组小鼠出现IBS‑D相关表现,包括粪便含水量和肠道敏感性增加,肠道传输时间缩短。实验组小鼠结肠组织中炎症因子包括IL‑Iβ、IL‑6、TNF‑α的表达水平升高(P<0.05)。另外,实验组小鼠结肠组织中NF‑κB、TLR4、MyD88的表达水平也高于对照组小鼠(P<0.05)。结论肠道菌群失调作为始发因素及重要驱动因素参与了IBS‑D的发生发展。菌群紊乱诱导的肠黏膜低度炎症及NF‑κB相关通路的异常激活可能在此过程中发挥关键作用。

Objective To investigate the role of intestinal flora in the development of irritable bowel syndrome with diarrhea(IBS‑D).Methods The mice treated with antibiotics were randomly assigned to experimental group or control group.IBS‑D mouse feces and normal mouse feces were given to the experimental group and control group for fecal microbiota transplantation,respectively.The fecal water content,intestinal transit time,and intestinal sensitivity were observed.qRT‑PCR was used to determine the mRNA expression of nuclear factor kappa‑B(NF‑κB),Toll like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),interleukin‑1β(IL‑Iβ),interleukin‑6(IL‑6),and tumor necrosis factorα(TNF‑α)in colon tissue.Western blotting was used to determine the protein levels of the above‑mentioned parameters.Results IBS‑D related symptoms presented in the mice of the experimental group,such as increased fecal water content and intestinal sensitivity,and shortened intestinal transit time.The expression levels of inflammatory factors(IL‑Iβ,IL‑6,and TNF‑α),NF‑κB,TLR4,and MyD88 in the colon tissue of experimental group were significantly higher than those in the control group(P<0.05).Conclusion Intestinal flora inbalance is involved in the development and progression of IBS‑D as an initiating important driver.Dysbiosis‑induced hypo‑inflammation of the intestinal mucosa and abnormal activation of NF‑κB‑related pathways may play key roles in this process.