摘要
目的 观察肠道微生态对腹泻型肠易激综合征(irritable bowel syndrome,IBS)的影响情况,探讨其可能的作用机制。方法 将32只SD大鼠均分为4组,每组8只。IBS-D组、益生菌组和TLR4拮抗剂组首先分别给予乙酸灌肠+束缚应激造模,同时益生菌组每日予70 mg/ml双歧杆菌三联活菌胶囊350 mg/(kg?d)灌胃,TLR4拮抗剂组予TLR4拮抗剂TAK-2423 mg/(kg?d)腹腔注射。空白对照组正常饲养。荧光定量PCR法测定各组大鼠肠道菌群含量,qRT-PCR法检测肠道上皮TLR4基因表达情况,ELISA法检测结肠组织匀浆中TNF-α及IL-10水平。结果 大便性状评分:IBS-D组和拮抗剂组均高于空白对照组,也均高于益生菌组,拮抗剂组低于IBS-D组;内脏敏感性评分:IBS-D组大鼠球囊容量均明显低于其它三组,且随着评分增加,IBS-D组大鼠球囊容量上升不明显,球囊容量为0.8 ml时,IBS-D组大鼠腹壁收缩次数明显高于其他三组大鼠;肠道菌群:IBS-D组和拮抗剂组大肠埃希菌和肠球菌含量均高于对照组,B/E比值均<1;TLR4表达:IBS-D组、益生菌组及拮抗剂组大鼠TLR4表达均高于对照组,益生菌组及拮抗剂组大鼠TLR4表达均低于IBS-D组;炎性因子:IBS-D组大鼠结肠组织中TNF-α水平均高于其他三组,IL-10水平明显低于其他三组;以上差异均有统计学意义(均P <0.05)。另外,益生菌组大鼠结肠组织中TNF-α和IL-10水平与对照组相当,拮抗剂组大鼠结肠组织中TNF-α水平与对照组相当,益生菌组与对照组各菌群含量相当,且B/E> 1,拮抗剂组大鼠TLR4表达与益生菌组相当,差异均无统计学意义(均P> 0.05)。结论 腹泻型IBS发生发展中,肠道微生态失调致病机制之一可能是活化TLR4,诱发产生炎性因子,增高内脏敏感性,进而产生或加重IBS症状。益生菌制剂可能通过调节肠道微生态,下调TLR4表达,改善肠道敏感性,从而缓解IBS患者腹痛与大便性状改变等症状。
Objectives To observe the effect of intestinal microbiota on diarrhea-predominant irritable bowel syndrome and explore its possible mechanism.Methods 32 male SD rats were divided into 4 groups.Acetic acid enema and restraint stress were given respectively to IBS-D group,probiotics group and TLR4 antagonist group.Meanwhile,the probiotic group was given intragastric administration with 70 mg/ml Bifidobacterium triple viable capsule 350 mg/(kg·d)daily,and the TLR4 antagonist group was given TLR4 antagonist TAK-242 3 mg/(kg·d)by intraperitoneal injection.Blank control group was normal feeded.The intestinal flora was analyzed by fluorescent quantificative PCR,the mRNA expression of TLR4 was detected by RT-PCR,and the levels of TNF-αand IL-10 were detected by ELISA.Results The Bristol stool scores of IBS-D group and antagonist group were significantly higher than blank control group and probiotics group,and antagonist group was lower than IBS-D group.The balloon volume of IBS-D group was significantly lower than the other three groups,and with the increase of AWR score,the balloon volume of IBS-D group did not increase significantly,and the number of abdominal contraction of IBS-D group was significantly higher than the other three groups when the balloon volume was0.8 ml.The abundance levels of E.coli and Enterococcus in IBS-D group and antagonist group were higher than control group,B/E<1;the expression levels of TLR4 in IBS-D group,probiotic group and antagonist group were higher than control group,and the expression levels of TLR4 in probiotic group and antagonist group were lower than IBS-D group.The level of TNF-αin IBS-D group was higher than the other groups,and the level of IL-10 was significantly lower than the other three groups(P<0.05).In addition,the levels of TNF-αand IL-10 in probiotic group were similar to control group,the level of TNF-αin antagonist group was similar to control group,the probiotic group and the control group had the same content of intestinal flora,B/E>1,and the expression level
作者
张杰
李红
王进海
邵珲
李永
杨龙宝
ZHANG Jie;LI Hong;WANG Jin-hai;SHAO Hui;LI Yong;YANG Long-bao(Department of Nuclear Medicine,the Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004,China;Department of Gastroenterology,the Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004,China;Department of Structural Cardiology,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)
出处
《世界临床药物》
CAS
2019年第5期340-346,共7页
World Clinical Drug
关键词
腹泻型肠易激综合征
肠道微生态
TOLL样受体4
炎性因子
diarrhea type irritable bowel syndrome
intestinal microbiota
Toll like receptor 4
inflammatory cytokines
