腹膜粘连的细胞机制研究进展_王睿鹏.pdf

版权归中国普通外科杂志所有http:/2023 年 1 月中国普通外科杂志Vol.32 No.1第 32 卷 第 1 期China Journal of General SurgeryJan.2023腹膜粘连的细胞机制研究进展王睿鹏1，李军良1，2（1.甘肃中医药大学第一临床医学院，甘肃 兰州 730030；2.甘肃省人民医院 普通外科，甘肃 兰州 730030）摘 要 腹膜粘连（PA）是由手术、腹膜炎症、腹膜透析等引起的腹腔内受损组织和器官间的异常纤维性粘连带，其中手术是引发 PA 的主要原因。PA 可引起不孕、肠梗阻、肠穿孔等临床并发症，二次松解手术为主要治疗方案，但易复发且存在多种并发症风险。近年来开发出一系列用于PA预防与治疗的药物和屏障材料，但防治效果尚不满意。抗PA药物会增加出血的风险，并抑制正常免疫功能，屏障材料虽然一定程度上缓解了 PA 进展，但因其不能持久覆盖腹膜损伤部位、降解不彻底等问题，不能达到抗 PA的理想效果。因此在 PA 防治上需要新的突破。近期的研究表明 PA 是一系列事件综合作用的结果，包括血管损伤、血小板聚集、凝血级联反应、纤维蛋白沉积等过程，最终纤维蛋白和细胞外基质沉积形成粘连带，后期形成收缩性瘢痕并引发临床症状，上述事件中，参与PA的各种细胞发挥了关键作用。腹膜微环境中分布有腹膜间皮细胞（PMC）、中性粒细胞、嗜酸性粒细胞、T淋巴细胞、巨噬细胞、肥大细胞等。生理条件下，这些细胞成分对腹膜微环境的动态稳定具有重要意义。当细菌和异物侵入腹膜腔时，纤维蛋白和炎性细胞随腹腔液渗出以限制、清除并吸收异物，最终纤维蛋白被吸收，腹膜损伤正常愈合。病理条件下，上述细胞功能紊乱，从而促进PA进展。PMC功能的失调促进初始PA形成、炎症反应扩大、纤维蛋白过度沉积；中性粒细胞和腹膜常驻巨噬细胞最早被募集到腹膜损伤部位，前者介导炎症反应，后者覆盖损伤部位起短暂保护作用；PA中晚期中性粒细胞形成中性粒细胞外陷阱并协同其他细胞促进纤维化进展导致 PA 形成。笔者就腹膜微环境中多种细胞在 PA 发生和发展中的作用机制，以及各种细胞在 PA 进展中的相互作用作一概述，此外介绍近年来防治 PA 的主要措施，并总结以参与PA的细胞为中心防治PA的策略，以期为临床防治PA提供新思路。关键词 组织黏连；腹膜；间皮细胞；炎症；纤维化；综述中图分类号：R656Research progress of cellular mechanisms in peritoneal adhesionsWANG Ruipeng1,LI Junliang1,2(1.The First School of Clinical Medical,Gansu University of Chinese Medicine,Lanzhou,730030,China;2.Department of General Surgery,Gansu Provincial Hospital,Lanzhou 730030,China)Abstract Peritoneal adhesions(PAs)are abnormal fibrous bands between damaged tissues and organs in the abdominal cavity caused by surgery,peritoneal inflammation,peritoneal dialysis,etc.Among them,文献综述 China Journal of General Surgery,2023,32(1):128-135.http:基金项目：甘肃省自然科学基金资助项目（20JR10RA372）；甘肃省卫生行业科研计划基金资助项目（GSWSKY-2019-03）；陇原青年创新创业人才基金资助项目（111266548053）；甘肃中医药大学科学研究与创新基金资助项目（2020KCYB-7）；甘肃省教育厅高校大学生就业创业能力提升基金资助项目（2021-6）。收稿日期：2022-08-01；修订日期：2022-11-04。作者简介：王睿鹏，甘肃中医药大学第一临床医学院本科生，主要从事腹膜相关疾病方面的研究。通信作者：李军良，Email:Ldoi:10.7659/j.issn.1005-6947.2023.01.012/dx.doi.org/10.7659/j.issn.1005-6947.2023.01.012128第 1 期王睿鹏，等：腹膜粘连的细胞机制研究进展 版权归中国普通外科杂志所有http:/surgery is the leading cause of PAs.PAs can cause infertility,intestinal obstruction,intestinal perforation,and other clinical complications.Secondary adhesiolysis surgery is the primary treatment option,but it is prone to recurrence and has various complications and risks.In recent years,a series of drugs and barrier materials have been developed to prevent and treat PAs,but the effect is not satisfactory.PA-resistant drugs increase the risk of bleeding and inhibit normal immune function.Although barrier materials can alleviate the progress of PAs to a certain extent,they cannot achieve the ideal effect of anti-PAs because they cannot cover the peritoneal injury site for a long time,and the degradation is not complete.Therefore,breakthroughs are needed in the prevention and treatment of PAs.Recent studies have shown that PAs result from various events,including vascular injury,platelet aggregation,coagulation cascade,and fibrin deposition.Eventually,fibrin and extracellular matrix deposition form adhesion bands and later develop contractile scarring and cause clinical symptoms.In the above events,various cells involved in PAs play a crucial role.Peritoneal mesothelial cells(PMCs),neutrophils,eosinophils,T lymphocytes,macrophages,mast cells,etc.,are distributed in the peritoneal microenvironment.Under physiological conditions,these cellular components are significant for the dynamic stabilization of the peritoneal microenvironment.When bacteria and foreign bodies invade the peritoneal cavity,fibrin and inflammatory cells exude with the peritoneal fluid to limit,remove,and absorb foreign bodies.Finally,the fibrin is absorbed,and the peritoneal injury usually heals.Under pathological conditions,the above cells are dysfunctional,promoting the progression of PAs.Dysfunction of PMC function promotes initial PA formation,expanded inflammatory response,and excessive fibrin deposition;neutrophils and peritoneal resident macrophages are first recruited to the peritoneal injury site,the former mediates the inflammatory response,and the latter covers the injury site for a transient protective effect;intermediate and advanced neutrophils of PAs form neutrophil extracellular traps and synergize with other cells to promote fibrosis progression and lead to PA formation.Here,the authors review the action mechanisms of various cells in the peritoneal microenvironment in the pathogenesis and development of PAs and the connections and interactions of multiple cells in the progression of PAs.In addition,the main measures for the prevention and treatment of PAs,which have been widely studied in recent years are introduced,and the prevention and treatment strategies focused on the cells involved in PAs are summarized,hoping to provide new ideas for the clinical prevention and treatment of PAs.Key words Tissue Adhesions;Peritoneum;Peritoneal Mesothelial Cells;Inflammation;Fibrosis;ReviewCLCCLC numbenumber r:R656腹 膜 粘 连（peritoneal adhesions，PA）是 由 手术、腹膜炎、腹膜透析等引起的腹腔中受损组织和器官间的异常纤维性粘连带1-3，其中手术后粘连最为常见，据报道4，术后有 50%90%的患者发生粘连。PA 可诱发慢性腹痛、急性肠梗阻、肠穿孔及女性不孕等问题5，PA 发生