Nevado Rebeca, Forcén Raquel, Layunta Elena, Murillo María Divina, Grasa Laura
Farmacología y Fisiología, Universidad de Zaragoza, España.
Farmacología y Fisiología, Universidad de Zaragoza. Facultad de Veterinaria, España.
Rev Esp Enferm Dig. 2015 Nov;107(11):672-6. doi: 10.17235/reed.2015.3868/2015.
Tight-junction (TJ) proteins regulate paracellular permeability. Gut permeability can be modulated by commensal microbiota. Manipulation of the gut microbiota with antibiotics like bacitracin and neomycin turned out to be useful for the treatment of diarrhoea induced by Clostridium difficile or chemotherapy drugs.
To evaluate the effects of the microbiota depletion evoked by the oral administration of neomycin and bacitracin on the intestinal permeability and expression of TJ proteins in mice.
Mice received neomycin and bacitracin orally for 7 days. Intestinal permeability was measured by the fluorescein-isothiocyanate-dextran (FITC-dextran) method. The gene expression of TJ proteins in the intestine was determined by real time-PCR.
FITC-dextran levels in serum were reduced by half in antibiotic-treated mice, indicating a reduction of intestinal permeability. Antibiotics increased the expression of zonula occludens 1 (ZO-1), junctional adhesion molecule A (JAM-A, and occludin in the ileum and ZO-1, claudin-3, and claudin-4 in the colon.
The combination of neomycin and bacitracin reduce intestinal permeability and increase the gene expression of ZO-1, junctional adhesion molecule A (JAM-A), and occludin in the ileum and ZO-1, claudin-3, and claudin-4 in the colon.
紧密连接(TJ)蛋白调节细胞旁通透性。肠道通透性可由共生微生物群调节。事实证明,用杆菌肽和新霉素等抗生素操纵肠道微生物群对治疗艰难梭菌或化疗药物引起的腹泻很有用。
评估口服新霉素和杆菌肽引起的微生物群耗竭对小鼠肠道通透性和TJ蛋白表达的影响。
小鼠口服新霉素和杆菌肽7天。通过异硫氰酸荧光素-葡聚糖(FITC-葡聚糖)法测量肠道通透性。通过实时PCR测定肠道中TJ蛋白的基因表达。
抗生素处理的小鼠血清中FITC-葡聚糖水平降低了一半,表明肠道通透性降低。抗生素增加了回肠中闭合蛋白1(ZO-1)、连接黏附分子A(JAM-A)和闭合蛋白的表达,以及结肠中ZO-1、紧密连接蛋白3和紧密连接蛋白4的表达。
新霉素和杆菌肽的组合降低了肠道通透性,并增加了回肠中ZO-1、连接黏附分子A(JAM-A)和闭合蛋白以及结肠中ZO-1、紧密连接蛋白3和紧密连接蛋白4的基因表达。