Herbs-partitioned moxibustion alleviates aberrant intestinal epithelial cell apoptosis by upregulating A20 expression in a mouse model of Crohn's disease  

作　　者：Jing Zhou Lu-Yi Wu Liu Chen Ya-Jing Guo Yi Sun Tao Li Ji-Meng Zhao Chun-Hui Bao Huan-Gan Wu Yin Shi 

机构地区：[1]Graduate School,Shanghai University of Traditional Chinese Medicine [2]Qigong Institute,Shanghai University of Traditional Chinese Medicine [3]Key Laboratory of Acupuncture and Immunological Effects,Shanghai University of Traditional Chinese Medicine [4]Key Laboratory of Acupuncture and Immunological Effects,Shanghai Institute of Acupuncture-Moxibustion and Meridian [5]Outpatient Department,Shanghai Institute of Acupuncture-Moxibustion and Meridian

出　　处：《World Journal of Gastroenterology》2019年第17期2071-2085,共15页世界胃肠病学杂志（英文版）

基　　金：Supported by National Natural Science Foundation of China,No.81273844 and No.81473757;National Key Basic Research Program of China(973 Program),No.2015CB554500;Shanghai Rising-Star Program,No.16QA1403400

摘　　要：BACKGROUND A20 inhibits intestinal epithelial cell apoptosis in Crohn's disease, and herbspartitioned moxibustion(HPM) has been demonstrated to be an effective treatment for Crohn's disease. However, the mechanism by which HPM reduces intestinal epithelial cell apoptosis in Crohn's disease has not been thoroughly elucidated to date.AIM To elucidate whether HPM exerts its effects by upregulating A20 to affect intestinal epithelial cell apoptosis in a Crohn's disease mouse model.METHODS In this study, mice with A20 deletion in intestinal epithelial cells(A20 IEC-KO) were utilized to establish a Crohn's disease mouse model with 2,4,6-trinitrobenzenesulfonic acid(TNBS) administration, as well as wild-type mice. Mice were randomly divided into normal control(NC), model control(MC), mesalazine(MESA), and HPM groups. The morphology of the colonic mucosa was observed by hematoxylin-eosin staining, and serum endotoxin and apoptosis of epithelial cells were evaluated by enzyme-linked immunosorbent assay and terminal dUTP nick-end labeling assay accordingly. The protein expression levels of A20 and tumor necrosis factor receptor 1(TNFR1)-related signaling molecules were evaluated by Western blot, and co-expression of A20 and TNFR1-associated death domain(TRADD) and co-expression of A20 and receptor-interacting protein 1(RIP1) were observed by double immunofluorescence staining.RESULTS The intestinal epithelial barrier was noted to have an improvement in the HPM group of wild-type(WT) mice compared with that in A20 IEC-KO mice. Compared with A20 IEC-KO HPM mice, serum endotoxin levels and apoptosis percentages were decreased(P < 0.01), A20 expression levels were increased(P < 0.01), and expression of TNFR1, TRADDD, and RIP1 was decreased in the HPM group of WT mice(PTNFR1 < 0.05, PTRADD < 0.01, PRIP1 < 0.01). Both of the co-expression of A20/TRADD and A20/RIP1 showed a predominantly yellow fluorescence in the HPM group of WT mice, while a predominantly red fluorescence was noted in the HPM group of A20 IEC-KO mice.CONCLUSIONBACKGROUND A20 inhibits intestinal epithelial cell apoptosis in Crohn's disease, and herbspartitioned moxibustion(HPM) has been demonstrated to be an effective treatment for Crohn's disease. However, the mechanism by which HPM reduces intestinal epithelial cell apoptosis in Crohn's disease has not been thoroughly elucidated to date.AIM To elucidate whether HPM exerts its effects by upregulating A20 to affect intestinal epithelial cell apoptosis in a Crohn's disease mouse model.METHODS In this study, mice with A20 deletion in intestinal epithelial cells(A20 IEC-KO) were utilized to establish a Crohn's disease mouse model with 2,4,6-trinitrobenzenesulfonic acid(TNBS) administration, as well as wild-type mice. Mice were randomly divided into normal control(NC), model control(MC), mesalazine(MESA), and HPM groups. The morphology of the colonic mucosa was observed by hematoxylin-eosin staining, and serum endotoxin and apoptosis of epithelial cells were evaluated by enzyme-linked immunosorbent assay and terminal dUTP nick-end labeling assay accordingly. The protein expression levels of A20 and tumor necrosis factor receptor 1(TNFR1)-related signaling molecules were evaluated by Western blot, and co-expression of A20 and TNFR1-associated death domain(TRADD) and co-expression of A20 and receptor-interacting protein 1(RIP1) were observed by double immunofluorescence staining.RESULTS The intestinal epithelial barrier was noted to have an improvement in the HPM group of wild-type(WT) mice compared with that in A20 IEC-KO mice. Compared with A20 IEC-KO HPM mice, serum endotoxin levels and apoptosis percentages were decreased(P < 0.01), A20 expression levels were increased(P < 0.01), and expression of TNFR1, TRADDD, and RIP1 was decreased in the HPM group of WT mice(PTNFR1 < 0.05, PTRADD < 0.01, PRIP1 < 0.01). Both of the co-expression of A20/TRADD and A20/RIP1 showed a predominantly yellow fluorescence in the HPM group of WT mice, while a predominantly red fluorescence was noted in the HPM group of A20 IEC-KO mice.CONCLUSION

关 键 词：Herbs-partitioned MOXIBUSTION Crohn's disease Apoptotic pathway Inflammation A20 

分 类 号：R574.62[医药卫生—消化系统] R-332[医药卫生—内科学]