miR-34a-5p调节Notch-1/Hes1通路对溃疡性结肠炎大鼠结肠组织炎症反应的影响OA

Objective:To investigate the effect of microRNA-34A-5p on the inflammatory response of colonic tissue in rats with ulcerative colitis(UC)by regulating the Notch-1/hairy and enhancer of split homo-log 1(Hes1)pathway.Methods:The interaction between miR-34a-5p and Notch-1 was verified by dual-luciferase reporter gene assay.UC rats were constructed using DSS solution.The rats with successful modeling were randomly separated into the UC group,the NC agomir group(tail vein injection of 30mg/kg NC ag-omir),the miR-34a-5p agomir group(tail vein injection of 30mg/kg miR-34a-5p agomir),and the JFC group(tail vein injection of 30mg/kg miR-34a-5p agomir+gavage 0.5 mg/kg JFC),18 rats in each group.Another 18 rats that drank the same amount of distilled water as the DSS solution were selected as the Ctrl group.The Ctrl group and the UC group received the same amount of distilled water through the tail vein and by gavage.The disease activity index(DAI)and colon mucosa damage index(CMDI)scores of UC rats in each group were evaluated.The mRNA expression in the colon tissue of UC rats was detected by qRT-PCR.HE staining was used to measure the histopathology of colonic tissue in UC rats.The levels of MPO,TNF-α,IL-1β and IL-6 in the colon tissue of UC rats were detected by ELISA kits.The apoptosis of colonic tissue cells in UC rats was detected by TUNEL method.Western blot was used to detect the protein expressions of Notch-1 and Hes1 in the colon tissue of UC rats.Results:The colonic tissue mucosa in the Ctrl group was in-tact.In the UC group and the NC agomir group,the colonic tissue mucosa was defective or shed,the glandu-lar arrangement was disordered,a large number of inflammatory cell infiltrations could be seen,and the his-topathological score increased(P<0.05).In the miR-34a-5p agomir group,the mucosal structure of colonic tissue was relatively intact,the glandular arrangement was more orderly,the infiltration of inflammatory cells was prominently reduced,and the histopathological score decreased(P<0.05).In the JFC group,the muco-sal structure injury of colonic tissue was further aggravated,the infiltration of inflammatory cells increased,and the histopathological score raised(P<0.05).MiR-34a-5p could target and negatively regulate Notch-1.The UC group had higher DAI score,CMDI score,apoptosis rate,MPO,TNF-α,IL-1β,IL-6,Notch-1 mRNA and protein,Hes1 mRNA and protein than the Ctrl group,and lower miR-34a-5p than the Ctrl group(P<0.05).The miR-34a-5p agomir group had lower DAI score,CMDI score,apoptosis rate,MPO,TNF-α,IL-1β,IL-6,Notch-1 mRNA and protein,Hes1 mRNA and protein than the UC group and NC ag-omir group,and higher miR-34a-5p than the UC group and NC agomir group(P<0.05).The JFC group had higher DAI score,CMDI score,apoptosis rate,MPO,TNF-α,IL-1β,IL-6,Notch-1 mRNA and pro-tein,Hes1 mRNA and protein than the miR-34a-5p agomir group(P<0.05).Conclusion:MiR-34a-5p can inhibit the inflammatory response in the colonic tissue of UA rats by suppressing the Notch-1/Hes1 path-way.