修回日期: 2022-04-20
接受日期: 2022-05-03
在线出版日期: 2022-06-28
肠屏障由机械屏障、化学屏障、免疫屏障及微生物屏障共同组成, 是机体抵御微生物入侵的重要防线. 肠屏障各组分在生理情况下相互协调, 维持肠道内外环境的稳态. 创伤失血性休克时, 肠道灌注不足、肠缺血再灌注损伤等诸多因素作用下肠屏障功能容易发生障碍, 可发生细菌易位, 内毒素入血等, 引发肠源性感染和多器官功能障碍, 甚至导致死亡. 当前, 国内外关于创伤失血性休克肠屏障功能损伤机制和防治措施有较多理念上的更新和技术进展. 本文拟结合本团队前期研究, 对此领域做一文献综述, 以期为临床上预防和治疗创伤后肠功能障碍相关疾病提供系统全面的理论体系.
核心提要: 创伤失血性休克时, 肠道是全身炎症反应持续以及器官功能衰竭的始动因素, 可发生细菌易位内毒素入血等, 引发肠源性感染和多器官功能障碍.因而亟需总结探讨创伤失血性休克患者的肠屏障功能损伤机制及防治策略.
引文著录: 陈方, 储诚南, 丁威威. 创伤失血性休克肠屏障功能损伤机制及防治的研究进展. 世界华人消化杂志 2022; 30(12): 547-554
Revised: April 20, 2022
Accepted: May 3, 2022
Published online: June 28, 2022
The intestinal barrier is composed of mechanical barrier, chemical barrier, immune barrier, and microbial barrier, which has an important role in defense against microbial invasion. The components of intestinal barrier coordinate with each other under physiological conditions to maintain the homeostasis of intestinal internal and external environment. In traumatic hemorrhagic shock, intestinal barrier function is prone to be impaired by intestinal hypoperfusion, intestinal ischemia-reperfusion injury, and many other factors. Bacterial translocation and endotoxin entry into the blood may occur, leading to enterogenic infection, multiple organ dysfunction, and even death. At present, there are many conceptual updates and technical progress on the mechanisms, prevention, and treatment of intestinal barrier function injury in traumatic hemorrhagic shock both at home and abroad. This paper intends to make a literature review in this field based on the previous research of our team, in order to provide a systematic and comprehensive theoretical system for the clinical prevention and treatment of post-traumatic intestinal dysfunction related diseases.
- Citation: Chen F, Chu CN, Ding WW. Mechanisms and prevention of intestinal barrier function damage in traumatic hemorrhagic shock. Shijie Huaren Xiaohua Zazhi 2022; 30(12): 547-554
- URL: https://www.wjgnet.com/1009-3079/full/v30/i12/547.htm
- DOI: https://dx.doi.org/10.11569/wcjd.v30.i12.547
社会经济的快速发展伴随着交通意外、自然灾害等各种原因导致的创伤日益增多, 其中失血性休克是创伤死亡的主要原因之一[1]. 近年来, 国内外学者对创伤失血性休克(traumatic hemorrhagic shock, THS)的病理生理和治疗策略进行深入研究, 提出损伤控制性复苏、允许性低血压等新的技术与理念, 为提高救治成功率做出极大贡献[2]. 肠道是血供丰富的靶器官, 对全身性缺血反应尤为敏感, THS纠正复苏后肠粘膜缺血再灌注损伤(ischemia reperfusion injury, IRI)以及扩大的炎症反应会加剧肠道及远隔脏器的损伤, 甚至发展为多器官功能障碍综合征(multiple organ dysfunction syndrome, MODS)[3]. 可以说在THS病理过程中, 肠道发生功能障碍是全身炎症反应持续时间延长以及器官功能衰竭的始动因素. 因此对于THS患者的肠道功能保护与治疗亟需研究探讨, 本文旨在回顾文献研究阐明THS肠屏障功能损伤机制, 梳理肠功能障碍防治的基本策略, 对创伤患者肠道功能保护、阻断肠源性感染以及防治远期并发症具有十分重要的意义, 也为后续相关研究的创新提供理论依据.
肠屏障由机械屏障、化学屏障、免疫屏障及微生物屏障共同组成. 各组分在生理情况下相互协调, 维持肠道内外环境的稳态.
机械屏障又称物理屏障, 由粘膜层上皮细胞组成, 相邻细胞间由紧密连接、粘附连接、桥粒和缝隙连接的连接结构形成完整的肠上皮结构[4,5]. 其中对肠道屏障功能影响最大的是紧密连接, 组成包括完整的膜蛋白claudin家族, MARVEL蛋白(tight junction associated MARVEL proteins, TAMPs)由occludin、tricellulin和MARVELD3组成, 免疫球蛋白超家族由蛋白连接粘附分子(junctional adhesion molecule, JAM)等组成, 以及细胞内支架蛋白[如闭锁小带(zonula occludens, ZO)][6]. 紧密连接蛋白不同的家族成员在肠道通透性中的调控功能不同, 一些具有封闭功能(claudin 1,3,5,11,14,19和tricellulin), 能降低紧密连接的通透性. 还有大量的claudin蛋白在紧密连接之间形成通道, 具有阳离子(如claudin 2, 10b, 和15)、阴离子(如claudin-10a和-17)的选择性, 可调控氯化钠和水的重吸收(如claudin 2)[7]. 部分支架蛋白如ZO-1, ZO-2和ZO-3等包含PDZ 结构域, 可直接与肌动蛋白结合将紧密连接复合体锚定在细胞骨架内, 与细胞极性和调节紧密连接功能密切相关[8].
化学屏障是指覆盖在肠上皮表面的粘液层, 含有粘蛋白、粘多糖、胃酸、胆汁、消化酶、溶菌酶等化学物质[9]. 肠道杯状细胞分泌的粘液含有糖蛋白和糖脂, 是细菌表面粘附受体类似物, 可竞争性抑制细菌进攻肠道细胞的靶点[10]. van der Post[11]等表明杯状细胞分泌的MUC2粘蛋白可增强肠道稳态抑制树突状细胞的炎症反应. 同时, 粘液层含有大量的抗菌肽且内层致密难以穿透, 可阻断细菌与肠上皮细胞接触. 胃壁细胞分泌的大量盐酸有利于杀灭或抑制微生物, 而胆汁中胆盐、胆酸与内毒素结合, 可直接抑制细菌生长和菌群易位来维持肠道内环境的稳定[12].
肠道免疫系统由三种不同的粘膜淋巴结构组成: 上皮、固有层和派尔斑(Peyer's patches), 构成完整的肠道免疫屏障. 研究发现上皮中的一类固有淋巴细胞(innate lymphoid cells, ILCs)可被激活并产生IL22, IL22在肠道感染期间可以促进体内稳态和愈合, 还能诱导上皮细胞产生RegⅢα, 并杀死革兰氏阳性细菌[13]. 肠道固有免疫细胞表面表达多种病原识别模式受体(pathogen-associated molecular patterns, PAMPs), 例如细胞表面的Toll样受体(Toll-like receptor, TLR), 细菌脂多糖能与TLR结合, 激活下游 NF-κB、MAPK通路, 产生大量炎症因子并进一步启动免疫反应[14]. 固有层由B细胞和T细胞组成, 派尔斑是产生SIgA的B细胞成熟的场所, 浆细胞分泌的SIgA通过结合抗原, 中和内毒素来限制细菌和毒素进入细胞内[15].
THS发生时, 全身血液重新分配, 肠道可将约30%的循环血量通过"自体输血"方式输送到体循环中, 以保证脑心肺重要器官的供血[19]. 此时肠上皮细胞因缺血水肿, 胞内线粒体及内质网等细胞器功能紊乱, 发生凋亡和坏死, 导致屏障功能受损[20,21]. 此外, 肠道缺血缺氧导致酸中毒, 可直接损伤细胞结构, 紧密连接断裂, 还使得细胞膜表面Na+-K+-ATP酶功能受损, 发生代谢障碍, 导致细胞膜通透性改变[22].
THS复苏后肠道血液恢复再灌注, 肠道发生IRI导致肠粘膜屏障破坏更严重, 细菌和内毒素进入血循环并波及远隔器官, 这种现象称为细菌易位(bacterial translocation, BT)[23]. 其中活性氧(reactive oxygen species, ROS)和一氧化氮(nitric Oxide, NO)在IRI中起关键作用. ROS是有毒分子, 超出机体清除能力可导致肠粘膜细胞损伤死亡. ROS产生机制如下: (1)黄嘌呤氧化环节生成氧自由基是ROS的初始来源, 肠道缺血缺氧时胞内ATP代谢为次黄嘌呤并大量堆积, 此外低氧刺激黄嘌呤脱氢酶转化为产生氧自由基的黄嘌呤氧化酶. 而在再灌注时, 随之而来的大量O2, 导致黄嘌呤氧化反应加速, ROS迅速增加[24]; (2)Ca2+是黄嘌呤脱氢酶转化为黄嘌呤氧化酶的关键离子, 肠缺血后细胞发生钙超载, 细胞膜Ca2+通透性增加, 依赖ATP的Ca2+泵功能障碍, 以及再灌注带来大量Ca2+, 都使黄嘌呤氧化酶增加, 继而ROS产生也进一步增加[25].
NO在肠IRI中扮演着细胞毒性和细胞保护的双重作用. NO在肠道中具有许多有益作用, 如清除氧自由基、维持正常血管通透性、减少白细胞粘附于肠系膜内皮细胞和抑制血小板聚集等[26]. 但炎症状态下诱导的iNOS产生大量NO和过氧亚硝酸盐并形成中间产物, 如NO2、N2O3,可导致重要生物大分子(如DNA、RNA、蛋白质和脂质)的硝化和亚硝化, 从而破坏其功能[26]. 也有证据表明, NO和过氧亚硝酸盐可作用于线粒体, 抑制细胞呼吸, 从而触发细胞凋亡.
THS时肠道细胞因缺血缺氧受损, 粘膜上皮释放大量炎症因子, 不同炎症因子相互作用并产生联级放大效应形成"炎症风暴", 发生促炎/抗炎平衡失调, 造成局部肠屏障功能障碍甚至全身炎症反应综合征(systemic inflammatory response syndrome, SIRS). 涉及的炎症因子包括肿瘤坏死因子(tumor necrosis factor, TNF)、白细胞介素(interleukin, IL)、干扰素(interferon, IFN)等. TNF-α主要由巨噬细胞产生可直接导致肠道粘膜上皮细胞坏死凋亡, 通过钙调蛋白途径激活肌球蛋白轻链激酶(myosin light chain kinase, MLCK)介导MLC磷酸化从而抑制紧密连接蛋白表达, 引发肠屏障功能障碍. 既往关于IL的研究主要聚焦于IL-1β, 研究证实IL-1β通过NF-κB、ERK1/2、P38、MAPK通路介导MLCK激活, 紧密连接蛋白表达受抑制, 引发肠屏障功能障碍[27]. 此外, IL-6在肠屏障功能中的作用存在分歧, 有研究表明IL-6通过MEK/ERK和PI-3K/Akt信号通路诱导Claudin-2表达改变, 增加肠道紧密连接对阳离子的通透性[28]. 而研究发现IL-6还可通过诱导肠上皮中主要中间丝蛋白-角蛋白的表达上调来发挥肠道屏障保护作用. IFN可通过多种通路机制引发肠上皮细胞功能障碍. IFN-γ通过激活腺苷单磷酸蛋白激酶(adenosine monophosphate-activated protein kinase, AMPK)通路, 导致ZO-1和occludin 的表达下降, 从而引发肠屏障功能障碍[29]. 此外, IFN-γ激活GTP酶(Ras homologus oncogenes GTPase), 上调Rho相关蛋白激酶(Rho-associated protein kinase, ROCK), 诱导Occludin、Clauidin-1、JAM等紧密连接蛋白转移到细胞膜内侧, 导致肠道通透性增加[30].
肠粘膜常暴露于多种来源的蛋白水解酶中, 包括丝氨酸蛋白酶、半胱氨酸蛋白酶、天冬氨酸蛋白酶和基质金属蛋白酶. 蛋白水解活性对于维持肠道免疫稳态、正常组织更新和肠道屏障的完整性至关重要. THS发生后, 肠道缺血缺氧导致肠屏障被破坏, 胰蛋白酶进入肠壁启动"自身消化", 随后胰蛋白酶和其他消化酶可能会进入体循环, 激活其他蛋白酶, 从而导致肺和其他远隔器官功能障碍[31]. 同时, THS导致肠上皮细胞产生的金属蛋白酶-9(matrix metalloproteinase 9, MMP-9)、解整合素金属蛋白酶17(A disintegrin and metalloproteinase 17, ADAM-17)过度激活, 活化的MMP-9分解粘膜细胞外基质中Ⅳ型胶原蛋白, 肠上皮细胞支持结构受损[32]. ADAM-17可将前体TNF转化为可溶性的TNF-α, 导致肠上皮细胞凋亡以及紧密连接蛋白结构破坏[33]. 此外, 肠上皮细胞表面存在大量蛋白酶激活受体(protease-activated receptors, PARs), PAR-1和PAR-2与炎症反应、肠道通透性和肠道运动调节有关. 活化的胰蛋白酶、类胰蛋白酶、MMP-9、ADAM-17以及凝血因子Ⅶa、Ⅹa均是内源性PAR-2激动剂, PAR-1和PAR-2的激活会刺激促炎症介质的释放. 肠上皮细胞局部PAR-2激活会导致细胞通透性增加、离子转运改变以及紧密连接蛋白分布变化从而进一步影响肠屏障功能[34].
中性粒细胞(polymorphonuclear neutrophils, PMNs)作为人体免疫系统的第一道防线, 是天然免疫应答的重要组成部分. 中性粒胞外诱捕网(neutrophil extracellular traps, NETs)是2004年发现的PMNs杀灭细菌的一种全新机制[35]. 在创伤发生时, 引发炎症反应的一个关键因素是内源性"危险信号"的激活, 称为损伤相关分子模式(damage-associated molecular patterns, DAMPs). 研究表明HMBG-1、线粒体DNA、热休克蛋白、S100蛋白等DAMPs在极短时间内可募集活化的PMNs至损伤部位, 分泌TNF-α、IL-1、IL-6等细胞因子, 引发SIRS并通过循环系统对肠粘膜造成广泛损害[36]. 既往在脓毒症、IRI以及THS动物模型中观察到NETs对肠粘膜屏障的损伤作用, 使用DNA酶(DNaseⅠ)靶向清除NETs后, 肠屏障损伤可以得到显著改善[37]. 本研究组前期研究发现: 在THS动物模型中, 发现肠道CitH3(NETs主要成分)升高, 肠道紧密连接蛋白水平降低, 持续活化PMNs释放过量的NETs加重全身炎症反应、诱发肠道微循环障碍, 最终导致肠粘膜屏障功能受损[38].
NETs参与THS肠屏障损伤的机制十分复杂. 首先, NETs的组分包括髓过氧化物酶、组蛋白、弹性蛋白酶及cfDNA, 都可直接损伤肠屏障. 例如瓜氨酸化组蛋白作为NETs的特征产物具有细胞毒性, 可诱导细胞坏死凋亡; 髓过氧化物酶以及弹性蛋白酶可损伤紧密连接蛋白, 导致屏障受损. 其次, NETs作为内源性DAMPs, 这种无菌性炎症性损伤可激活先天免疫, 此外炎症会损伤毛细血管内皮细胞导致血管通透性改变、微血栓形成, 影响肠绒毛微循环, 加重肠粘膜缺血缺氧, 损伤肠屏障. 最后, NETs会引发大量炎症介质释放、补体系统激活, 趋化更多炎性免疫细胞向损伤的肠粘膜浸润, 造成更严重组织损伤[39]. 目前对于THS中NETs对肠屏障损伤的具体作用机制尚未完全阐明, 有待进一步探究. 本研究组前期研究证实在脓毒症模型中NETs可能通过促进炎症和细胞凋亡导致肠屏障功能障碍, 而抑制TLR9-ER应激信号通路可以改善NETs诱导的肠上皮细胞死亡[40].
生理状况下, 肠道内健康菌群与宿主共生保持相对稳态从而形成肠道的微生物屏障, 而严重THS会导致肠道菌群紊乱, 继而增加机会致病菌感染的风险. 肠致病性大肠杆菌(Enteropathogenic Escherichia coli, EPEC)感染可引起典型的肠道病变, EPEC使用Ⅲ型分泌系统(type 3 secretion system, T3SS)将细菌致病效应蛋白注入宿主细胞质, 控制细胞器的功能, 重新排列细胞骨架和膜通道, 并破坏细胞间紧密连接[41]. 此外, 研究表明感染肠侵袭性大肠埃希杆菌(Enteroinvasive Escherichia coli, EIEC)后, Caco-2细胞跨上皮电阻(transepithelial electrical resistance, TEER)下降, 并导致Claudin-1、Occludin、JAM-1和ZO-1蛋白的表达和重排受损, 引起细胞骨架蛋白F-actin的损伤, 影响紧密连接蛋白的结构和分布[42]. 肠道作为大量菌群驻扎地, 当THS发生时肠屏障受损导致BT发生, 大量细菌及内毒素入血, 诱发SIRS及脓毒症等严重并发症. 内毒素是革兰阴性杆菌细胞壁的成分对宿主肠屏障具有毒性作用, 其机制可表现为: 直接损伤肠上皮细胞, 导致绒毛损伤、细胞凋亡和肠道通透性的增加[43]. 同时可通过激活MLCK途径介导的MLC磷酸化, 下调紧密连接蛋白表达, 导致肠道通透性增加[44]. 内毒素诱导肠上皮细胞产生多种炎症因子如TNF-α、IL-1等, 激活补体系统, 产生炎症级联反应损伤肠屏障. 此外, PMNs的激活, 诱导ROS产生增多以及NETs生成在内毒素损伤肠屏障中也起着重要作用.
肠屏障是机体抵御外界危险环境, 阻止肠腔内的细菌、病毒、抗原、毒素等有害物质进入机体的一道重要防线, 因而改善受损肠道屏障功能的治疗措施具有重要的意义.
腹膜复苏(direct peritoneal resuscitation, DPR)是通过腹腔穿刺的方式将液体注入腹膜腔内的新型液体复苏方法, 其在改善微循环、增加脏器血流、减轻组织器官水肿及抑制全身炎症反应等方面具有重要价值[45,46]. DPR液是由高渗葡萄糖及丙酮酸盐组成的透析液, 其高渗性能有效减轻腹腔器官水肿, 而丙酮酸盐是一种有效的抗氧化剂和氧自由基清除剂[47]. 在THS和脓毒症大鼠模型中, 研究显示DPR降低肠道炎症因子水平, 如 IL-1、IL-6、TNF-α, 这表明DPR不仅增加肠道循环, 也降低肠道白细胞的趋化聚集, 减轻炎症反应[48]. Matheson等人[49]研究也发现对比DPR复苏组, 常规静脉复苏组细胞损伤标志物血清透明质酸(hyaluronic acid, HA)和HMGB1水平显著升高, 表明DPR可以减少炎症介质产生, 并有助于肠道通透性的维持. 目前DPR的发展仍在起步阶段, DRP的提出对临床上治疗THS、减轻肠屏障功能障碍提供了新的治疗思路.
远端缺血预处理(remote ischemic conditioning, RIC)是指对远程器官或组织(如四肢或肠道)进行短暂的缺血再灌注处理, 进而通过触发各种保护途径保护某些靶器官免受IRI的有害影响. 目前RIC的研究已证实具有几种有益的局部和全身效应, 包括通过降低基质金属蛋白酶活性、上皮细胞凋亡、粘膜损伤、中性粒细胞浸润、下调促炎因子, 上调抗炎因子来抵御损伤过程中的炎症阶段[50]. Czigany等人[51]的研究结果显示在全肝缺血大鼠模型中, RIC可发挥减轻远端肝细胞损伤以及减轻因严重充血和功能性缺血引起的肠道损伤的双重保护作用, 其机制主要为RIC可减少线粒体氧化应激及细胞内钙超载, 更好保存或增加ATP生成. 另一研究报道发现, 肢体RIC可导致循环抗炎和促炎细胞因子(包括IL-10、IL-６、MCP-1和TNF-α)的上调和下调, 继而减轻随后的肠道屏障损伤, 防止BT的发生[52]. 在坏死性小肠结肠炎(necrotizing enterocolitis, NEC)模型中, RIC可改善肠道微循环紊乱, 减轻肠道损伤, 延长存活时间[53]. 而目前IRC在THS所导致的肠屏障功能障碍中仍缺乏效果评估及相关机制的研究. 但因RIC有益的保护作用(全身的抗炎作用及改善肠屏障功能), 仍是在THS发生后治疗肠道IRI的潜在治疗选择.
肠内营养可降低致病菌的毒力作用, 有助于维持肠屏障功能, 提升机体免疫力[54]. 在创伤、烧伤和脓毒症诱导的休克动物模型中, 早期提供肠内营养可促进肠蠕动, 改善肠粘膜微循环, 激活肠道碱性磷酸酶的产生, 改善肠道和肝脏的组织灌注及氧供, 调控肠道菌群减少BT的发生. 在大鼠IR模型中, 肠内营养具有改善杯状细胞功能和紧密连接蛋白表达作用, 可能通过下调NF-κB/HIF-1α通路发挥抗凋亡和抗炎作用[55]. 此外, 对比肠外营养来说, 肠内营养能提升肠道内SIgA分泌水平. 从临床实践结果研究表明, 创伤患者早期使用肠内营养与肠外营养随机对照试验显示肠内营养能显著降低感染并发症的发生. 临床上, 患者若能够安全耐受肠内营养, 可考虑早期逐量进行肠内营养.
谷氨酰胺(glutamine, GLN)在传统意义上被认为是一种非必需氨基酸, 而在创伤、烧伤、营养不良等应激情况下体内GLN会被耗竭, 可以认为GLN是炎症和应激状态下的"条件性必需"氨基酸[56]. GLN的缺乏导致绒毛萎缩, 紧密连接蛋白的表达降低, 肠通透性增加. 研究表明在动物模型中, 肠外营养中GLN使得肠腔内MUC2和溶菌酶增加, IL-4、IL-10和IL-13显著增加, 降低细菌入侵水平, 有助于保护肠粘膜屏障[57]. 在IRI模型中, GLN是应激时肠粘膜的主要代谢营养素, 促进肠道SIgA生成, 稳定粘膜免疫防御抵御病原菌定植和内毒素侵袭[58]. GLN发挥保护肠屏障的可能机制有: GLN通过增加胞内谷胱甘肽(glutathione, r-glutamyl cysteingl +glycine, GSH)提高肠上皮细胞抗氧化能力, GSH直接或通过谷胱甘肽过氧化物酶催化作用清除生成的ROS. 此外, GLN可通过 ERK、NF-κB通路调节紧密连接蛋白分布, 抑制ZO-1表达下调, 增强肠道屏障功能[59].
丝氨酸蛋白酶抑制剂, 如萘莫司他(Nafamostat)和氨甲环酸(Tranexamic acid, TXA), 会抑制肠道内丝氨酸蛋白酶的活性, 抑制对肠道粘液层损害, 保护肠屏障[60,61]. 研究表明Nafamostat减少了THS诱导的肠道和肺损伤, 并限制了THS时肠系膜淋巴激活PMNs的能力. 此外, 研究发现TXA在肠腔内可抑制消化蛋白酶并保护肠道, 主要通过ADAM-17和TNF-α抑制syndecan-1的分泌实现[62]. 而本研究组发现在THS动物模型中, 早期静脉注射TXA可降低肠道中性粒细胞浸润, 抑制NETs释放, 减轻NETs相关肠屏障损伤[38]. 现今TXA对肠粘膜屏障的保护作用主要在动物实验中证实, 但仍需临床前瞻性试验来验证TXA预防THS肠屏障损伤这一新治疗思路的效果.
在THS条件下, 应用益生菌及其代谢产物, 能有效竞争性抑制致病菌的繁殖, 限制致病菌与肠上皮接触、定植, 保护肠屏障; 还可增加巨噬细胞或NK细胞的活性, 调节免疫球蛋白或细胞因子的分泌来促进肠道免疫屏障功能的恢复[63]. Cui等[64]研究筛选出双歧杆菌(FL-276.1和FL-228.1)具有增加TEER值, 抑制LPS刺激的NO、TNF-α和IL-6的产生, 发挥保护肠屏障和抗炎的作用. 在一项关于创伤患者使用益生菌的随机对照实验结果显示, 使用益生菌可有效降低呼吸机相关性肺炎、肠源性感染以及ICU住院时间[65]. 研究认为, 适当补充硒可以调节肠道微生物群影响肠屏障, Chen等人[66]研究出一种新的富硒益生菌, 将硒元素与益生菌的有利作用结合来保护由棒曲霉素诱导的小鼠空肠损伤. 然而根据目前对于益生菌对肠屏障保护作用机制结果呈现, 仍有待进一步研究.
THS导致的肠屏障损伤机制涉及多个领域多个方面, 本综述阐明现阶段各因素损伤肠屏障功能机制, 并总结肠功能障碍防治策略, 以期完善临床上预防和治疗创伤后肠功能障碍理论基础并为临床提供治疗策略及精确治疗的靶点可能. 近年来学者们通过细胞动物实验及临床研究对THS肠屏障功能损伤机制进行延续与补充, 并不断探索发现新兴机制, 并在治疗方法与理念革新方面取得了丰硕成果. 但仍存在许多机制未明的领域还需进一步深入研究, 针对肠道微循环、肠道菌群功能及其产物等具有前景的研究领域, 是未来研究应重点关注的, 以期能开发治疗THS导致肠屏障功能障碍的新疗法.
学科分类: 胃肠病学和肝病学
手稿来源地: 江苏省
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