Protective Effects of Bifidobacterium on Intestinal Barrier Function in LPS-Induced Enterocyte Barrier Injury of Caco-2 Monolayers and in a Rat NEC Model.

Zonulin protein is a newly discovered modulator which modulates the permeability of the intestinal epithelial barrier by disassembling intercellular tight junctions (TJ). Disruption of TJ is associated with neonatal necrotizing enterocolitis (NEC). It has been shown bifidobacterium could protect the intestinal barrier function and prophylactical administration of bifidobacterium has beneficial effects in NEC patients and animals. However, it is still unknown whether the zonulin is involved in the gut barrier dysfunction of NEC, and the protective mechanisms of bifidobacterium on intestinal barrier function are also not well understood. The present study aims to investigate the effects of bifidobacterium on intestinal barrier function, zonulin regulation, and TJ integrity both in LPS-induced enterocyte barrier injury of Caco-2 monolayers and in a rat NEC model. Our results showed bifidobacterium markedly attenuated the decrease in transepithelial electrical resistance and the increase in paracellular permeability in the Caco-2 monolayers treated with LPS (P < 0.01). Compared with the LPS group, bifidobacterium significantly decreased the production of IL-6 and TNF-α (P < 0.01) and suppressed zonulin release (P < 0.05). In addition, bifidobacterium pretreatment up-regulated occludin, claudin-3 and ZO-1 expression (P < 0.01) and also preserved these proteins localization at TJ compared with the LPS group. In the in vivo study, bifidobacterium decreased the incidence of NEC from 88 to 47% (P < 0.05) and reduced the severity in the NEC model. Increased levels of IL-6 and TNF-α in the ileum of NEC rats were normalized in bifidobacterium treated rats (P < 0.05). Moreover, administration of bifidobacterium attenuated the increase in intestinal permeability (P < 0.01), decreased the levels of serum zonulin (P < 0.05), normalized the expression and localization of TJ proteins in the ileum compared with animals with NEC. We concluded that bifidobacterium may protect against intestinal barrier dysfunction both in vitro and in NEC. This protective effect is associated with inhibition of proinflammatory cytokine secretion, suppression of zonulin protein release and improvement of intestinal TJ integrity.

Study on the establishment of rat model of different degree of diffuse axonal injury / 重庆医学

Objective To establish the different degrees of rat diffuse axonal injury (DAI) model by using a self‐made DAI device .Methods A total of 70 healthy adult clean SD rats were selected and randomly divided into the normal control group (n=10) and DAI group (n=60) ,then the DAI group was randomly subdivided into the group A ,B ,and C ,20 cases in each group .The rat head injury model was prepared by using the self‐made experimental device ,which made the rat head to simultaneously produce instant oversized linear and angular accelerations ,different degrees of rat DAI model ,including mild DAI(group A) ,moderate DAI (group B) and severe DAI(group C) ,were induced by different rotation back and forth ,accelerated movement times under the con‐stant air pressure .The pathological and behavior effect evaluation was performed .Results With the injury degree aggravating ,the time interval of nerve physiological reflex recovery and awakening time in the acute DAI groups were increased (P<0 .05) .The nerve function score after 7 d in the DAI groups was decreased (P<0 .05);the death rates within 14 d after injury in the group A , B and C were 5 .0% ,25 .0% and 50 .0% respectively .With the injury degree aggravating ,the DAI pathological characteristics were more significant .Conclusion This device could effectively establish different injury degrees of DAI animal model .