基于HMGB1/TLR4/PKR通路探讨松果菊苷对重症急性胰腺炎肠道黏膜屏障损伤的修复机制  

Repair mechanism of Echinetin on intestinal mucosal barrier damage in severe acute pancreatitis based on HMGB1/TLR4/PKR pathway

作　　者：张满鹤 于克静 贾世浩 张福梅 郝景察 ZHANG Manhe;YU Kejing;JIA Shihao;ZHANG Fumei;HAO Jingcha(Department of Emergency,Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine,Cangzhou,Hebei 061001,China;Department of Function,Yanshan People′s Hospital,Cangzhou,Hebei 061300,China;Department of Emergency,Yanshan County People′s Hospital,Cangzhou,Hebei 061300,China)

机构地区：[1]河北省沧州中西医结合医院急诊科,河北沧州061001 [2]河北省盐山县人民医院功能科,河北沧州061300 [3]河北省盐山县人民医院急诊科,河北沧州061300

出　　处：《国际检验医学杂志》2025年第2期146-150,156,共6页International Journal of Laboratory Medicine

基　　金：河北省中医药管理局中医药类科研项目(2022236)。

摘　　要：目的探讨松果菊苷(ECH)预处理对减轻重症急性胰腺炎(SAP)引起的肠道屏障功能障碍的影响。方法将36只大鼠随机分为Sham组、SAP组和SAP+ECH组,每组12只。采用胰管逆行注射3%牛磺胆酸钠诱导胰腺炎。对实验大鼠胰腺进行组织学检查,判断大鼠胰腺炎模型是否构建成功。通过大鼠肠道病理评分、血清二胺氧化酶(DAO)活性和内毒素水平,以及肠系膜淋巴结细菌易位率检测评估肠屏障功能。采用荧光定量PCR(qPCR)和蛋白质印迹(Western blot)检测紧密连接蛋白ZO-1和occludin的mRNA和蛋白表达水平,通过Western blot检测高迁移率组框1蛋白(HMGB1)、Toll样受体4(TLR4)和蛋白激酶R(PKR)表达水平。结果ECH对胰腺的组织学变化无明显影响,但可改善与SAP相关的肠黏膜屏障损伤和膜通透性。虽然ECH不影响SAP大鼠的回肠组织ZO-1和occludin的mRNA表达水平,但可明显增加ZO-1和occludin蛋白表达水平,并且ECH处理可明显降低SAP大鼠回肠HMGB1、TLR4和PKR蛋白表达水平。结论ECH可以减轻SAP诱导的体内肠道屏障功能障碍,其对肠道屏障功能的影响可能与抑制HMGB1/TLR4/PKR通路有关。Objective To explore the effect of Echinetin(ECH)pretreatment on alleviating intestinal barrier dysfunction caused by severe acute pancreatitis(SAP).Methods Totally 36 rats were randomly divided into Sham group,SAP group and SAP+ECH group,with 12 rats in each group.Pancreatitis was induced by retrograde injection of 3%sodium taurocholate into pancreatic duct.Histological examination was performed on the pancreas of experimental rats to determine whether the pancreatitis model of rats was successfully constructed.Intestinal barrier function was evaluated by intestinal pathological scores,serum diamine oxidase(DAO)activity and endotoxin levels,and bacterial translocation in mesenteric lymph nodes.The mRNA and protein expression levels of tight junction proteins ZO-1 and occludin were detected by quantitative fluorescent PCR(qPCR)and Western blot,and the protein expression levels of high mobility frame-1 protein(HMGB1),Toll-like receptor 4(TLR4)and protein kinase R(PKR)were detected by Western blot.Results ECH had no significant effect on the histological changes of pancreas,but could improve the intestinal mucosal barrier damage and membrane permeability associated with SAP.Although ECH does not affect the mRNA expression levels of ZO-1 and occludin in ileum of SAP rats,it could significantly increase the expression levels of ZO-1 and occludin,and ECH treatment could significantly reduce the expression levels of HMGB1,TLR4 and PKR in ileum of SAP rats.Conclusion ECH can reduce the intestinal barrier dysfunction induced by SAP,and its effect on intestinal barrier function may be related to the inhibition of the HMGB1/TLR4/PKR pathway.

关 键 词：松果菊苷 HMGB1/TLR4/PKR通路 重症急性胰腺炎 肠道黏膜 

分 类 号：R576[医药卫生—消化系统]