BOC2抑制N-甲酰肽/甲酰肽受体信号通路减轻SAP炎症损伤的机制研究

扫码查看

原文链接

NETL
NSTL
万方数据

中文摘要：目的观察BOC-Phe-Leu-Phe-Leu-Phe(BOC2)对重症急性胰腺炎(SAP)大鼠血中6种线粒体N-甲酰肽(NFPs)及胰腺组织中2种甲酰肽受体(FPRs)表达的影响,探讨其减轻SAP炎症损伤的机制.方法将40只雄性SD大鼠随机分为4组:假手术组,模型组,BOC2低、高剂量组(分别为0.1、0.2 mg/kg),每组10只.后3组以胆胰管逆行注射5%牛磺胆酸钠(50 mg/kg)制备SAP模型.造模结束后0.5 h腹腔注射相应剂量药物,4 h取材.苏木精-伊红染色观察胰腺病理改变;蛋白免疫印迹法检测血浆中NFPs的表达;免疫组化法检测胰腺FPRs表达;酶联免疫吸附试验检测血浆中白细胞介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-α水平;实时荧光定量聚合酶链反应检测胰腺局部组织炎性因子的表达.结果与模型组比较,BOC2低、高剂量组胰腺出血、腺泡细胞坏死、炎性细胞浸润、水肿等病理现象均改善;胰腺病理评分,血浆线粒体NADH-泛素氧化还原酶链(MT-ND)1、MT-ND2、MT-ND3、MT-ND5、MT-ND6表达,胰腺FPRs表达,血浆及胰腺组织中3种炎性因子表达均下降(P＜0.05).结论 BOC2可通过拮抗线粒体NFPs/FPRs信号通路减少炎性因子产生,减轻SAP炎症损伤.

外文标题：Mechanism study of BOC2 alleviating SAP inflammatory damage by inhibiting N-formyl peptide/formyl peptide receptor pathway

外文摘要：Objective To observe the effect of BOC-Phe-Leu-Phe-Leu-Phe(BOC2)on the expression of six types of mitochondrial N-formyl peptides(NFPs)in blood and two formyl peptide receptors(FPRs)in pancreatic tissue of rats with severe acute pancreatitis(SAP),and to explore its mechanism of alleviating inflammatory damage of SAP.Methods Forty male SD rats were randomly divided into four groups:the sham group,the SAP model group,the BOC2 low-dose and the BOC2 high-dose group(0.1 and 0.2 mg/kg),with 10 animals in each group.The SAP model was prepared by retrograde injection of 5%sodium taurocholate(50 mg/kg)into biliary and pancreatic ducts in the last 3 groups.BOC2 was intraperitoneally injected at 0.5 hours after SAP modeling,and samples were taken 4 hours after modeling.HE staining was used to observe pathological changes in pancreas.Western blot assay was used to detect the expression of NFPs in plasma.IHC staining was used to detect the expression of FPRs in pancreatic tissue.ELISA was used to detect interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α levels in plasma.qPCR was used to detect expression levels of inflammatory factors in local pancreatic tissue.Results Compared with the model group,the BOC2 high-dose group and the BOC2 low-dose group showed improvement in pathological phenomena,such as pancreatic bleeding,acinar cell necrosis,inflammatory cell infiltration and edema.The pancreatic injury score,pancreatic FPRs expression,plasma MT-ND1,MT-ND2,MT-ND3,MT-ND5,MT-ND6 expression,as well as expression levels of three inflammatory factors in plasma and local pancreatic tissue,were significantly reduced(P＜0.05).Conclusion BOC2 can reduce the production of inflammatory factors and alleviate SAP inflammatory damage by antagonizing mitochondrial NFPs/FPRs signaling pathway.

外文关键词：

pancreatitisN-formylmethionine leucyl-phenylalaninereceptors,formyl peptidemitochondriaBOC2severe acute pancreatitis

作者：

张桂贤、刘大卫、李文畅、蔡隽、宗文辉、刘洪斌、赵秀梅

展开 >

作者单位：

天津市医药科学研究所(邮编 300020)

天津市和平区卫生健康委员会

关键词：

胰腺炎 N-甲酰甲硫氨酰亮氨酰-苯丙氨酸受体,甲酰肽线粒体 BOC2 重症急性胰腺炎

基金：

国家自然科学基金资助项目天津市科学技术局重点项目天津市科学技术局面上项目天津市科学技术局青年项目天津市卫生健康科技项目天津市卫生健康科技项目

项目编号：

8230479721JCZDJC0122021JCYBJC0168023JCQNJC00600TJWJ2022MS049TJWJ2024MS047

出版年：

2024

DOI：

10.11958/20240774

天津医药

天津市医学科学技术信息研究所

天津医药

CSTPCD

影响因子：1.107

ISSN：0253-9896

年,卷(期)：2024.52(10)