Study on Correlation Between Nuclear Receptors and Outcome of Rats with Ulcerative Colitis
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Graphical Abstract
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Abstract
OBJECTIVE To investigate the correlation between the expression of related nuclear receptors in colonic tissues and the outcome of rats with ulcerative colitis(UC). METHODS Serum and colon tissues were collected from SD rats druing UC acute stage and UC recovery stage which were induced by one-time colon perfusion of 2,4,6-trinitrobenzene sulfonic acid(TNBS). Disease activity index and fecal water content were calculated to investigate the pathological changes of the colon, so as to evaluate the rat UC model. Plasma tumor necrosis factor(TNF-a), interferon-g(IFN-g), interleukin 4(IL-4) and IL-13 were determined by ELISA. Colorimetric method was used to detect the activity of colonic myeloperoxidase(MPO). Real-time PCR was used to determine the mRNA expression of farnesoid X receptor(FXR), pregnane X receptor(PXR), constitutive androstane receptor(CAR), peroxisome proliferators activate receptor g(PPARg). R software assessed the correlation between nuclear receptors and inflammatory factors. RESULTS The disease activity index and fecal water content of rats in the model group decreased significantly, indicating the success establishment of UC rat model. Compared with the normal control group, the mRNA expression levels of FXR, CAR and PPARg in the colon of rats in the acute stage of UC group were significantly decreased, while the contents of plasma TNF-a and IFN-g were significantly negatively correlated with them(P<0.05), IL-4 was significantly positively correlated with FXR; colonic PXR expression level was decreased, which was not correlated with inflammatory factors; in addition, the plasma MPO content in rats increased, which was negatively correlated with PPARg(P<0.05). Compared with the acute inflammatory stage of UC group, the levels of plasma proinflammatory factors TNF-a, IFN-g, and plasma MPO activity were significantly decreased in the recovery stage of UC group(P<0.05), while the levels of plasma anti-inflammatory factors IL-4 and IL-13 were significantly increased(P<0.05), and the mRNA expression levels of colon FXR, PXR, CAR, and PPAR were significantly increased(P<0.05). CONCLUSION The colonic nuclear receptors FXR, CAR and PPAR in UC rats are correlated with the outcome of UC rats.
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