| Objective: To explore the protective effect of 4-PBA on the intestinal mucosal barrier during UC in rats.Methods: At the overall animal level,by establishing a trinitrobenzene sulfonic acid(TNBS)-induced UC animal model,SPD rats were randomly divided into control group,UC model group,4-PBA treatment group,each 10 rats in the group;the control group was routinely fed,given the same dose of 0.9% sodium chloride solution enema to make a pseudomembrane type,without any special treatment;the UC model group continued to be routinely fed after the model was completed,by intraperitoneal injection Give 0.9% sodium chloride solution(50mg / kg)for 3 consecutive days;4-PBA treatment group is given intraperitoneal injection of molecular chaperone 4-PBA on the basis of UC model daily at a therapeutic dose of 50 mg / kg for 3 consecutive days Administration.After modeling,begin to observe the animal's appearance,mental state,activity,diet,stool,disease activity index(DAI),etc.;after 2 weeks,the animal's heart is blood sampled and the serum is separated at room temperature,and the serum AST,ALT,Scr,lactic acid kit to detect serum D-lactic acid(D-LA),diamine oxidase kit to determine serum diamine oxidase(DAO)content,ELISA kit to detect serum tumor necrosis factor-?(TNF-?)Equal expression level,cut about 6 cm of colon tissue about 3 cm away from the anal margin of SPD rats,observe the ulcer index(UI)score,fix formaldehyde at the same time,make paraffin sections,HE staining,and observe colon pathology under microscope Changes and scores of colonic gross morphological injury(CMDI)and histological injury index(TDI).SPSS22.0 statistical software was used for statistical data analysis,and the difference was statistically significant with two-sided P <0.05.Result:(1)The three groups of SPD rats in the control group,UC model group and4-PBA treatment group were in good condition before modeling,and no obvious abnormalities were found.After modeling,the UC model group gradually showed irregular hair color,mental depression,anorexia and less movement,diarrhea and loosestools,and weight loss.After the 4-PBA treatment group was given a molecular chaperone(4-PBA),the general condition gradually improved,the coat color was smooth,the spirit was good,the eating was basically normal,the stool was softer,and the weight did not decrease significantly,which was significantly improved compared with the UC model group.(2)The control group,UC model group,and 4-PBA treatment group all took blood from the heart after 2 weeks and separated the serum at room temperature,and analyzed the expression levels of serum AST,ALT,Scr,D-LA,DAO,TNF-?,etc.The indexes of the UC model group showed a significant upward trend compared with the control group,and the indexes of the 4-PBA treatment group showed a downward trend compared with the UC model group,and the difference in the index analysis was statistically significant(P <0.05).(3)The control group,UC model group,and 4-PBA treatment group all took a colonic specimen after 2 weeks,and analyzed the scores of DAI,CMDI,TDI,and UI.It was found that the UC model group had a significantly higher score than the control group.The 4-PBA treatment group had a significantly lower score than the UC model group,and the score between the groups was statistically significant(P <0.05).Pathological pictures showed that the SPD rats in the control group had normal colon morphology and clear structure,and no obvious inflammation was seen.Cell infiltration;mucosal edema was seen in the colon tissue of the UC model group,part of the intestinal mucosa was necrotic and shed,goblet cells were reduced,a large number of inflammatory cells were infiltrated,and the structure of the gland was disordered;Infiltration of inflammatory cells is significantly reduced.Conclusion: In the course of the development of UC,ulcerative colitis rats are accompanied by a series of processes such as intestinal mucosal damage and increased permeability,which leads to the damage of the intestinal mucosal barrier.However,the administration of molecular chaperone4-PBA can reduce the inflammation of intestinal mucosa tissue,thereby reducing The permeability of the damaged intestinal mucosa achieves the protection of the intestinal mucosa barrier.It can prevent the deterioration of UC disease and prevent the occurrence of complications,enrich the theoretical understanding of UC intestinal mucosal injury,provide experimental work foundation for the treatment of clinical UC and intestinal mucosal barrier protection,and further provide research reference for the prevention and treatment of severe intestinal mucosal barrier. |
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