Nuclear receptor relieve pathological injury of ulcerative colitis by FXR regulating the endoplasmic reticulum stress pathway in vivo
Objective To explore the effect of farnesoid X receptor(FXR)activation on the pathological damage of colon tissue in ulcerative colitis(UC)model mice and its mechanism.Methods Forty healthy C57BL/6 male mice were randomly divided into control group,model group,obeticholic acid(OCA)group,and obeticholic acid+tunicamycin(OCA+TM)group.The weighed,the fecal characteristics and the degree of occult blood,the disease activity index(DAI),and colon length were recorded.The serum levels of IL-1β,IL-6 and TNF-α in mice in each group were detec-ted by ELISA.HE staining was used to observe the pathological changes of colon tissue of mice in each group.Immuno-histochemical staining was used to detect the positive expression of GRP78 and CCAAT/CHOP in colon tissue of mice in each group.RT-qPCR and Western blotting were used to detect the expression changes of GRP78 and CHOP at the mR-NA and protein levels in colon tissue of mice in each group.Results Compared with the control group,the DAI of mice in the model group was increased.The length of the colon was shorter,and the contents of IL-1β,IL-6 and TNF-α in the serum were increased.The colon tissue was significantly damaged,and extensive inflammatory cell infiltration was seen in the colon.The positive staining of GRP78 and CHOP in the tissue was enhanced.The relative mRNA and pro-tein expressions of GRP78 and CHOP were up-regulated(P<0.05).Compared with the model group,the DAI of mice in the OCA group was decreased,and the length of the colon was increased.The contents of IL-1β,IL-6 and TNF-α in the serum were decreased.The damage degree of the colon tissue was significantly improved,and infiltrating inflammatory cell was not found in the colon tissue.The positive staining of GRP78 and CHOP was weakened,and the relative mRNA and protein expressions of GRP78 and CHOP were down-regulated(P<0.05).Compared with the OCA group,the DAI of mice in the OCA+TM group was increased while the length of the colon was shortened,and the contents of IL-1β,IL-6 and TNF-α in the serum also increased.The colon tissue was damaged,showing obvious ulceration.At the same time,the positive staining of GRP78 and CHOP in colon tissue was enhanced.The relative mRNA and protein expres-sions of GRP78 and CHOP were also up-regulated(P<0.05).Conclusion Activating FXR in UC mice model can ef-fectively alleviate the pathological damage of colon tissue,and the mechanism may be related to the regulation of endo-plasmic reticulum stress pathway.
Ulcerative colitisFarnesoid X receptorObeticholic acidEndoplasmic reticulum stress
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