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| Base on YAP/TAZ Signaling Pathway to Investigate the Effect of Atractylenolide I on Intestinal Barrier Dysfunction in UC Rats |
| LI Sen, TIAN Lihui, HAN Tao, et al |
| Handan Central Hospital, Hebei Handan 056000, China |
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Abstract Objective: To investigate the effects of atractylenolide I (Atr-I) on intestinal barrier dysfunction and Yes-associated protein (YAP)/transcription coactivator containing PDZ binding motif (TAZ) signaling pathway in rats with ulcerative colitis (UC).Methods: UC rat model was constructed,all experimental rats were divided into UC group,17.5,35.0 mg/kg Atr-I dose group (Atr-I-L,Atr-I-H group),35.0 mg/kg Atr-I+17.5 mg/kg Yap inhibitor vitipofin group (Atr-I-H+VTPF group),18 rats in each group,and 18 rats were taken as control group (Control group).After the experiment,the body weight of mice of each group was measured and the disease activity index (DAI) was calculated after intervention.The length of the colon was measured and the pathological morphology changes of the colojisun in each group were observed by hematoxylin-eosin (HE) staining.Serum interleukin (IL)-1β,IL-17 and interferon-γ (IFN-γ) were detected with enzyme-linked immunosorbent assay (ELISA).The positive expression of intestinal mucosal barrier-related protein band-closing protein 1 (ZO-1) and claudin-1 (Claudin-1) in colon tissue of rats of each group were detected by immunohistochemistry.The protein expression levels of YAP,p-YAP and TAZ in colon tissues were detected by western blotting (Western blot).Results: Compared to Control group,the colonic mucosal epithelial cells in UC group were disordered,the goblet cells were significantly reduced,a large amount of infiltration inflammatory cells were found,and ulcers were formed in some areas,even thickening and adhesion,intestinal deformation,mucosal congestion and edema were obvious,body weight,colon length,ZO-1,Claudin-1 positive expression,p-YAP/YAP,and TAZ expression were significantly decreased,and the DAI score,IL-1β,IL-17,and IFN-γ levels were obviously increased (P<0.05).Compared with UC group,the colonic mucosal epithelial injury of rats in Atr-I-L and Atr-I-H groups was improved,body weight,colon length,positive expression of ZO-1,Claudin-1,p-YAP/YAP and TAZ were significantly increased in turn,and the DAI score,IL-1β,IL-17 and IFN-γ levels were significantly decreased in turn (P<0.05).Compared with Atr-I-H group,the colonic mucosal epithelial injury in Atr-I-H+VTPF group was aggravated,body weight,colon length,ZO-1,Claudin-1 positive expression,p-YAP/YAP,and TAZ expression were significantly decreased,and the DAI score,IL-1β,IL-17,and IFN-γ levels were obviously increased (P<0.05).Conclusion: Atr-I can reduce DAI score,inhibit inflammatory response,improve colonic mucosal epithelial injury,and improve intestinal barrier dysfunction in UC rats,the mechanism may be related to the activation of YAP/TAZ signaling pathway.
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2024, Vol. 30 
