Honokiol Prevents Intestinal Barrier Dysfunction in Mice with Severe Acute Pancreatitis and Inhibits JAK/STAT1 Pathway and Acetylation of HMGB1

作     者：LI Jie CHEN Ya-feng GAO Lei LI Yi-jie FENG Dian-xu 

作者机构：Department of General SurgeryPutuo HospitalShanghai University of Traditional Chinese MedicineShanghai200062China 

出 版 物：《Chinese Journal of Integrative Medicine》 (中国结合医学杂志（英文版）)

年 卷 期：2024年第30卷第6期

页      面：534-542页

核心收录：

学科分类：1006[医学-中西医结合] 1002[医学-临床医学] 10[医学] 100602[医学-中西医结合临床] 

基　　金：Supported by National Natural Science Foundation of China(No.81803920 and 81673789) Key Medical Specialty Construction Project of Shanghai Municipal Health Commission(No.ZK2019B18) Shanghai Putuo District Health Commission Characteristic Disease Construction Project(No.2020TSZB03)。 

主　　题：severe acute pancreatitis intestinal barrier dysfunction honokiol high-mobility group protein B1 Januskinase signal transducerand activatorof transcription1 

摘      要：Objective To investigate the effect of honokiol(HON)and the role of high-mobility group protein B1(HMGB1)on the pathogenesis of severe acute pancreatitis(SAP).Methods Thirty mice were numbered according to weight,and randomly divided into 5 groups using a random number table,including control,SAP,SAP and normal saline(SAP+NS),SAP and ethyl pyruvate(SAP+EP),or SAP+HON groups,6 mice in each group.Samples of pancreas,intestine,and blood were collected 12 h after SAP model induction for examination of pathologic changes,immune function alterations by enzyme linked immunosorbent assay(ELISA),and Western blot.In vitro experiments,macrophages were divided into 5 groups,the control,lipopolysaccharide(LPS),LPS+DMSO(DMSO),LPS+anti-HMGB1 monoclonal antibody(mAb),and LPS+HON groups.The tight connection level was determined by transmission electron microscopy and fluorescein isothiocyanate-labeled.The location and acetylation of HMGB1 were measured by Western blot.Finally,pyridone 6 and silencing signal transducer and activator of the transcription 1(siSTAT1)combined with honokiol were added to determine whether the Janus kinase(JAK)/STAT1 participated in the regulation of honokiol on HMGB1.The protein expression levels of HMGB1,JAK,and STAT1 were detected using Western blot.Results Mice with SAP had inflammatory injury in the pancreas,bleeding of intestinal tissues,and cells with disrupted histology.Mice in the SAP+HON group had significantly fewer pathological changes.Mice with SAP also had significant increases in the serum levels of amylase,lipase,HMGB1,tumor necrosis factor-α,interleukin-6,diamine oxidase,endotoxin-1,and procalcitonin.Mice in the SAP+HON group did not show these abnormalities(P0.01).Studies of Caco-2 cells indicated that LPS increased the levels of occludin and claudin-1 as well as tight junction permeability,decreased the levels of junctional adhesion molecule C,and elevated intercellular permeability(P0.01).HON treatment blocked these effects.Studies of macrophages indicated that LPS led to low nuclear levels of HMGB1,however,HON treatment increased the nuclear level of HMGB1(P0.01).HON treatment also inhibited the expressions of JAK1,JAK2,and STAT1(P0.01)and increased the acetylation of HMGB1(P0.05).Conclusion HON prevented intestinal barrier dysfunction in SAP by inhibiting HMGB1 acetylation and JAK/STAT1 pathway.