Effect Of β-carotene On Ulcerative Colitis And Liver Damage In Mice

As a barrier against pathogens,the intestine is easily stimulated by external factors to produce endoplasmic reticulum stress,inflammation and other phenomena,which makes the secretion of inflammatory cytokines in the body unbalanced,leads to an inflammatory cascade reaction in the body and causes damage to the liver or other tissues and organs through the gut-liver axis,and ultimately causes the occurrence of diseases.In the process of inflammation,nuclear receptors can inhibit inflammation signal pathways and regulate the expression of inflammatory cytokines and cytochrome P450 enzymes in the liver.Our research group has been researching and discussing the antioxidant,and immunity enhancement of β-carotene for a long time,but the role of PXR/NF-κB signaling pathway in inflammation has not yet been clarified.In this experiment,the intestine and liver are regarded as a whole,and a mouse model of ulcerative colitis was established by drinking3% DSS solution,and the gut-liver axis was used to explore the effect of β-carotene on liver damage caused by ulcerative colitis through the PXR/NF-κB signaling pathway,and analyze the regulatory effects of β-carotene on related inflammatory indicators.We randomly divided 80 Kunming male mice 6～7 weeks old with similar body weight into 8groups,each with 10 mice,which were set as: control group,50mg/kg β-carotene group,100mg/kg β-carotene group,200mg/kg β-carotene group,DSS group,DSS +50mg/kg β-carotene group,DSS +100mg/kg β-carotene group,DSS +200mg/kg β-carotene group.DSS was processed by dissolving DSS powder in purified water to prepare a 3% mass fraction of DSS drinking solution for mice to drink,and the drinking method of mice was not restricted,and the corresponding concentration of β-carotene was given to the stomach every day.The test period is 7days.The experimental results were showed below:(1)Through the measurement of growth indexes and blood biochemical indexes,it was found that the colon length,body weight and CYP450 activity in the serum of the DSS group were significantly lower than those of the control group(P<0.05);DAI score,liver index,and LPS,TNF-α,IL-6,IL-1β,AST,and ALT levels in the serum were significantly higher than those of the control group(P<0.05);the comparison results of DSS+β-carotene and DSS group showed an opposite trend,and IL-1β had no significant difference(P>0.05)).It can be preliminarily judged that DSS has successfully induced ulcerative colitis in mice by using landmark indicators such as colon length and DAI score.β-carotene can improve this phenomenon.At the same time,it is speculated that β-carotene may have a positive effect on liver damage caused by mice drinking 3%DSS solution.(2)We observed under the microscope that the crypt structure of the colon of the DSS group was deformed,mucus secretion was reduced,and inflammatory infiltration appeared,which was consistent with the histological characteristics of ulcerative colitis.Subsequently,The expression levels of TNF-α,IL-6,IL-1β,NF-κB,IRE1,XBP1 in the mouse colon were detected,and we found that compared with the DSS group,these related indexes of the DSS+β-carotene group were significantly reduced(P<0.05),indicating that β-carotene can relieve endoplasmic reticulum stress by inhibiting the activation of NF-κB p65 and IRE1,and effectively reduce the expression of inflammatory cytokines to improve DSS-induced ulcerative colon inflammation.(3)We observed the morphological changes of the liver tissue under the microscope,and found that the liver cells in the liver tissue of the DSS group were disorderly arranged,structurally abnormal,cytoplasmic loose,hepatic cords arranged irregularly,and a variety of cells of different sizes were mixed,the internal structure of the liver lobules is disordered and there is inflammatory infiltration,indicating that the mice drinking DSS solution caused liver damage.Simultaneously,The SOD activity,MDA content,and the expression of TNF-α,IL-6,IL-1β,CYP1A2,CYP2E1,CYP3A11,PXR,NF-κB p65 in the liver of mice were tested to explore the effect of β-carotene on liver damage caused by ulcerative colitis.The results showed that compared with the DSS group,the MDA content,TNF-α,IL-6,IL-1β and NF-κB p65 expression levels in the liver of the DSS+β-carotene group were significantly reduced(P<0.05),the gene expression level of CYP1A2,CYP2E1,CYP3A11,SOD activity,and the protein expression of CYP3 A and PXR were significantly increased(P<0.05),indicating that β-carotene may increase the gene expression of CYP1A2,CYP2E1,CYP3A11 through the PXR /NF-κB pathway,and reduce the expression level of inflammatory cytokines to effectively improve the liver damage caused by DSS-induced ulcerative colitis.Based on the above research results,we can conclude that β-carotene can improve the histomorphological damage of colon and liver caused by drinking DSS solution,inhibit the activation level of NF-κB p65 and IRE1,On the basis of the gut-hepatic axis,increase the expression of PXR and cytochrome P450 enzymes in the liver through the PXR/NF-κB pathway,regulate the secretion and expression of inflammatory cytokines,and thereby alleviate colonic inflammation and liver damage caused by ulcerative colitis.This study uses nuclear receptors PXR to regulate the expression of inflammation-related indicators to alleviate the inflammatory response,which provides new ideas for reducing the occurrence of inflammation and provides a theoretical basis for the production and utilization of β-carotene.