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Retardant effect of dihydroartemisinin on ulcerative colitis in a JAK2/STAT3-dependent manner

查看全文 作  者:Mingrui [1,2]Jiang;Guangjun [3]Zhong;Yichao [4,5]Zhu;Liuhua [1]Wang;Yuzhe [2]He;Qiannan [1]Sun;Xiaoqing [2]Wu;Xiaolan [6]You;Sujun [1]Gao;Dong [1]Tang;Daorong [1,5]Wang 高影响力作者 机构地区:[1]Department of General Surgery,General Surgery Institute of Yangzhou,Northern Jiangsu People’s Hospital,Clinical Medical College,Yangzhou University,Yangzhou 225001,China;[2]Medical College of Yangzhou University,Yangzhou 225001,China;[3]Baoying People’s Hospital,Yangzhou 225800,China;[4]Department of Physiology,Nanjing Medical University,Nanjing 211166,China;[5]Yangzhou Clinical Medical School,Nanjing Medical University,Northern Jiangsu People’s Hospital,Yangzhou 225001,China;[6]Department of Gastrointestinal Surgery,Taizhou People’s Hospital,Taizhou 225300,China高影响力机构 出  处:《Acta Biochimica et Biophysica Sinica》索引2021年第53卷第9期,共11页高影响力期刊 基  金:the grant from the State Key Laboratory of Cancer Biology(Air Force Medical University of PLA)(No.CBSKL201716). 摘  要:Dihydroartemisinin(DHA)is a semi-synthetic derivative and the main active metabolite of artemisinin.The purpose of this study was to investigate the effect of DHA on the ulcerative colitis(UC)in both in vivo and in vitro models.Weight,survival rate,colon length,and Disease Activity Index score were used to evaluate the severity of colitis.Reverse transcription quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to detect the expressions of cytokines interleukin(IL)-1,IL-1β,IL-4,IL-6,IL-10,IL-12,and tumor necrosis factor-α(TNF-α).The expressions of Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3),and the phosphorylation of JAK2(p-JAK2)and STAT3(p-STAT3),were measured by western blot analysis.Western blot analysis and immunohistochemistry were used to detect the expressions of tight junction proteins.We found that the weights and colon lengths of mice in dextran sodium sulfate(DSS)+DHA group were significantly lower and longer than those in the DSS group,respectively.Compared with those in the DSS group,the expressions of IL-1β,IL-6,IL-17,and TNF-αin the DSS+DHA and DSS+5-aminosalicylic acid(5-ASA)groups were decreased,while the expressions of IL-4 and IL-10 were significantly upregulated.DHA largely increased the expressions of zonula occludens-1 and occludin.Western blot analysis and/or immunohistochemical staining analysis showed that the expressions of JAK2,STAT3,p-JAK2,and p-STAT3 in DSS+DHA and DSS+5-ASA groups were significantly lower than those in DSS group.DHA has a specific therapeutic effect on UC.The anti-inflammatory mechanism of DHA is related to the blockage of the JAK2/STAT3 signaling pathway.These findings provide evidence that DHA may be a useful drug and is expected to become a promising new treatment for human UC. 关 键 词:DIHYDROARTEMISININ DSS-induced colitis JAK2/STAT3 signal ulcerative colitis
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