Study on the protective effect of Xiaoxianxiong decoction on 5-fluorouracil-induced intestinal damage in mice
Objective:To investigate how Xiaoxianxiong decoction can protect against intestinal damage caused by 5-fluoroura-cil(5-FU)in mice.Methods:One hundred male ICR breed mice with SPF-grade were randomised into the normal control group,the model group and the low,medium and high dose(8.3,16.6 and 33.2 g/kg)groups of Xiaoxianxiong decoction.Intestinal mu-cosal injury was induced in all groups,except the control group,by administering 5-FU(30 mg/kg,ip,7 d).While modeling was ongoing,the mice in the Xiaoxianxiong decoction group were administered 10 mL·kg-1·d-1 via gavage,following the prescribed dos-age.The control and model groups were administered equal volume of distilled water and treated continuously for 7 d.Histopatho-logical alterations in the small intestine were assessed utilizing hematoxylin-eosin staining(HE),with the villus height to crypt depth ratio(VH:CD)subsequently determined.The number of goblet cells in the small intestinal mucosa was determined by Al-cian blue staining(AB).The concentrations of endotoxin(ET)and D-lactic acid(D-LA)in serum were measured using spectro-photometry,along with diamine oxidase(DAO)levels in the small intestine.The levels of interleukin-6(IL-6)and tumor necro-sis factor-α(TNF-α)in serum were detected using enzyme-linked immunosorbent assay(ELISA).The mRNA expression of IL-6,signal transducer and activator of transcription 3(STAT3),and epidermal growth factor receptor(EGFR)was detected us-ing reverse transcription quantitative polymerase chain reaction(RT-qPCR).The IL-6,STAT3 and EGFR protein were expres-sion in small intestinal tissues were detected by the Western blot method.Results:Compared to the control group,the model group of mice presented a significant reduction in body mass and an increase in scores for diarrhoea,faecal mass,faecal water con-tent,and small intestinal propulsion rates.(P<0.01).The VH:CD ratio,as well as the number of goblet cells in the small intesti-nal mucosa,exhibited a noteworthy decrease(P<0.01).The levels of ET and D-LA in the serum significantly augmented,while the level of DAO in the small intestine was significantly decreased(P<0.05).Significant reductions were observed in the indices for the spleen and thymus(P<0.01).A significant increase was observed in the serum levels of IL-6 and TNFα(P<0.05).IL-6 and STAT3 mRNA expression were significantly up-regulated,whilst EGFR mRNA expression was down-regulated in small bowel tissues(P<0.01).The expression of IL-6 and STAT3 proteins was found to be significantly higher,while that of EGFR proteins was significantly lower,in small intestinal tissues(P<0.01).Compared to the model group,Xiaoxianxiong decoction led to a significant improvement in the aforementioned indices(P<0.05).Conclusion:Xiaoxianxiong decoction can safeguard the in-testinal mucosa against damage caused by 5-FU.The mechanism of action may involve the activation of EGFR signalling,down-regulation of the IL-6/STAT3 signalling pathway,reduction of 5-FU-induced inflammation of the intestinal mucosa,and improvement of immune function.
Xiaoxianxiong decoction5-fluorouracil(5-FU)Intestinal mucosal injuryEpidermal growth factor receptor(EGFR)Interleukin 6(IL-6)/signaling and activator of transcription 3(STAT3)signaling pathway
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