運動對腸道屏障和黏膜免疫穩(wěn)態(tài)影響的研究進展

吳 嵽，陳佩杰，羅貝貝

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運動對腸道屏障和黏膜免疫穩(wěn)態(tài)影響的研究進展

吳 嵽，陳佩杰，羅貝貝

上海體育學(xué)院 運動科學(xué)學(xué)院, 上海 200438

腸道屏障和黏膜免疫穩(wěn)態(tài)是機體抵御外來病原微生物入侵的重要防線。運動過程中血液重新分配，消化系統(tǒng)血液灌流量減少，腸道處于低氧環(huán)境，誘導(dǎo)轉(zhuǎn)錄因子低氧誘導(dǎo)因子（hypoxia-inducible factor, HIF）-1α持續(xù)表達，參與調(diào)節(jié)腸黏膜免疫穩(wěn)態(tài)。相關(guān)研究證明，中小強度運動有助于腸黏膜免疫穩(wěn)態(tài)的維持，而大強度運動損傷腸道屏障，破壞腸黏膜免疫穩(wěn)態(tài)。通過回顧腸道屏障結(jié)構(gòu)基礎(chǔ)及黏膜免疫機能相關(guān)研究報道，綜述不同強度運動對腸道屏障功能和黏膜免疫穩(wěn)態(tài)的影響，進一步討論HIF-1α在運動對腸道屏障功能和黏膜免疫穩(wěn)態(tài)的調(diào)節(jié)中所起的關(guān)鍵作用，為運動與腸道屏障功能和黏膜免疫相關(guān)研究提供新思路。

腸道屏障；黏膜免疫；運動；低氧誘導(dǎo)因子-1α

運動過程中機體的血液重新分配，內(nèi)臟血流量減少，容易導(dǎo)致腸黏膜缺血，腸通透性增加、細菌易位及內(nèi)毒素產(chǎn)生[13]，可能是運動員出現(xiàn)胃腸道癥狀（gastrointestinal symptoms）[26]的主要原因[100]，主要表現(xiàn)為腹痛、腹瀉甚至胃腸道出血。

不同運動強度和持續(xù)時間對腸道屏障和黏膜免疫機能的影響各異。定期的適度運動可能會降低機體感染發(fā)生率，有研究報道，適度運動能減輕腸道炎癥反應(yīng)，且不會影響正常的腸黏膜屏障組織結(jié)構(gòu)與形態(tài)[53]。然而，長時間的劇烈運動可導(dǎo)致機體免疫系統(tǒng)暫時性紊亂，并在運動后持續(xù)24 h左右[63,66]，主要表現(xiàn)為嗜中性粒細胞的呼吸爆發(fā)、淋巴細胞的增殖、自然殺傷細胞活性降低等，并引起腸道屏障功能受損、黏膜免疫穩(wěn)態(tài)變化。運動過程中腸道屏障缺氧程度加劇，導(dǎo)致低氧誘導(dǎo)因子（hypoxia-inducible factor, HIF）-1α穩(wěn)定表達，可能對腸黏膜免疫穩(wěn)態(tài)的改變起到了一定作用。盡管通常情況下優(yōu)秀運動員不存在免疫缺陷，但是，免疫指標的小幅變化也將對訓(xùn)練和比賽成績造成較大影響。因此，了解運動如何影響腸道屏障功能和黏膜免疫穩(wěn)態(tài)，以及在該過程中HIF如何發(fā)揮作用，有助于運動員合理安排訓(xùn)練，預(yù)防減輕胃腸道癥狀。

目前，腸黏膜屏障已成為生物醫(yī)學(xué)界的研究熱點，Hooper L V[36]和Duerkop B A[19]等對腸黏膜屏障相關(guān)研究進行了詳細的綜述，也有很多報道深入研究了HIF的功能與轉(zhuǎn)錄調(diào)控機制[20,43,77,78,80]，這些研究為進一步了解運動對腸道屏障功能和黏膜免疫穩(wěn)態(tài)的影響提供了理論與實驗基礎(chǔ)。本文將簡要介紹腸黏膜屏障的結(jié)構(gòu)基礎(chǔ)及免疫機能，闡述不同強度運動對腸黏膜屏障功能的影響，以及HIF在這些影響中可能的作用機制，為運動與腸道屏障功能和黏膜免疫相關(guān)研究提供新思路。

1 腸黏膜屏障的結(jié)構(gòu)基礎(chǔ)及免疫機能

腸黏膜屏障是機體屏障系統(tǒng)的重要部分，按功能可分為化學(xué)、機械、生物和免疫屏障[2]?；瘜W(xué)屏障分泌各種活性物質(zhì)，保護腸道黏膜。機械屏障通過細胞連接，阻擋病原微生物入侵。大量共生菌群定植在腸黏膜表面，形成生物屏障。正常情況下，腸道共生菌群保持相對穩(wěn)定；病理情況下，細菌及代謝產(chǎn)物結(jié)構(gòu)與數(shù)量失衡，病原微生物可穿透生物屏障。免疫屏障通過黏膜相關(guān)淋巴組織及各種免疫活性成分維持腸道正常的免疫機能（圖1）。

1.1 腸黏膜屏障的結(jié)構(gòu)基礎(chǔ)

黏液素、抗菌肽和溶菌酶共同構(gòu)成了腸黏膜化學(xué)屏障。腸上皮表面杯狀細胞（goblet cell）分泌大量黏液素（mucins，MUC）形成黏液層。黏液層由15～30 μm的黏液內(nèi)層和100～400 μm的黏液外層構(gòu)成[58]。在黏液外層中，黏液素與菌群相互作用，抵御病原微生物入侵。生理情況下，在人和小鼠腸道中表達的主要是分泌型黏液素MUC2及膜型黏液素MUC13和MUC17[40,46]。Van der Sluis M等發(fā)現(xiàn)，MUC2缺失導(dǎo)致小鼠腸黏膜形態(tài)異常，表現(xiàn)為腸上皮細胞扁平化和局部潰瘍，腸黏膜屏障功能受損，引發(fā)炎癥反應(yīng)[91]。在黏液內(nèi)層中的抗菌肽和溶菌酶主要溶解細菌胞壁、破壞細菌胞膜完整性[81]?？咕闹饕笑?防御素（α-defensin）和再生胰島衍生蛋白（regenerating islet-derived protein，Reg）3γ[53]。α-defensin由潘氏細胞（Paneth cell）分泌至隱窩腔[16]。在嚙齒類動物腸道中，α-defensin也被稱為隱窩素（cryptidins）。Reg3γ由腸上皮細胞分泌，是一種C型凝集素，起到限制細菌與腸上皮接觸的作用[90]。腸蠕動時，黏液素、抗菌肽和溶菌酶協(xié)同發(fā)揮抑菌作用，及時清除入侵病原微生物，并協(xié)助修復(fù)損傷的腸上皮細胞。

圖1 腸黏膜屏障的結(jié)構(gòu)

Figure1. Structure of Intestinal Mucosal Barrier

腸上皮細胞間的緊密連接（tight junction）構(gòu)成了腸黏膜機械屏障（圖2）。緊密連接主要由連接黏附分子的閉合蛋白（occludin）和緊密連接蛋白（claudins）以及細胞內(nèi)的閉合小帶蛋白（zonula occludens）ZO-1、ZO-2、ZO-3構(gòu)成[8]，能將腸上皮細胞連接在一起，阻止大分子和細菌透過。物質(zhì)通過緊密連接主要經(jīng)由膜孔途徑（the pore pathway）和泄漏途徑（the leak pathway）[23]。膜孔途徑依賴于鈣黏蛋白（E-Cadherins）和緊密連接蛋白[5]，是不帶電荷的溶質(zhì)和小分子（半徑＜4 A）透過緊密連接的主要途徑。泄漏途徑依賴于ZO-1和occludin[51,89,92,93]，只允許少量大分子物質(zhì)（＞10 kDa）包括脂多糖（lipopolysaccharide，LPS）在內(nèi)通過緊密連接[98]。當腸上皮細胞間緊密連接受損時，膜孔途徑與泄漏途徑異常開放，腸黏膜屏障通透性病理性升高，大量病原微生物與外來抗原物質(zhì)透過腸黏膜屏障，從而啟動腸黏膜屏障的免疫防御機能[57]。

1.2 腸黏膜屏障的免疫機能

腸黏膜免疫系統(tǒng)（mucosal immune system）是由腸上皮細胞及其分泌物、黏膜相關(guān)淋巴組織和棲息菌群構(gòu)成，是機體抵御腸腔內(nèi)病原微生物入侵的第一道防線。

腸黏膜免疫系統(tǒng)通過濾泡相關(guān)上皮（follicular-associated epithelium，F(xiàn)AE）和樹突狀細胞（dendritic cell，DC）對抗原不斷地進行識別，防止病原微生物入侵[54]。正常情況下，腸固有層（lamina propria）中存在的大量效應(yīng)性和記憶性淋巴細胞對無害抗原保持低應(yīng)答或者無應(yīng)答狀態(tài)。病理情況下，病原微生物入侵腸固有層，活化DC等抗原提呈細胞，刺激免疫細胞和感染組織分泌多種細胞因子，發(fā)揮非特異性免疫效應(yīng)，誘導(dǎo)急性期反應(yīng)。

圖2 腸上皮細胞間的緊密連接

Figure2. The Intestinal Epithelium and Tight Junction

腸上皮細胞中的模式識別受體（pattern recognition receptor，PRR）可識別病原微生物的病原相關(guān)分子模式（pathogen-associated molecular patterns，PAMP），區(qū)分外來的病原微生物和宿主共生菌[45]。當機體檢測到病原相關(guān)分子模式，模式識別受體與病原相關(guān)分子模式相互作用可迅速激活效應(yīng)細胞，促進對外來病原微生物的清除。在腸黏膜免疫系統(tǒng)中的模式識別受體主要為腸上皮細胞表面的Toll樣受體（Toll-like receptors）[68]和胞漿中的Nod樣受體（Nod-like receptors）。模式識別受體可使機體在腸黏膜屏障發(fā)生廣泛的感染之前，快速檢測識別病原微生物[12,15,34,84,88]，對腸黏膜屏障的免疫監(jiān)視和局部穩(wěn)態(tài)維持起著重要的作用。

分泌型免疫球蛋白A（secretory immunoglobulin A，SIgA）也是腸黏膜屏障免疫機能的重要組成部分。免疫球蛋白A（immunoglobulin A，IgA）由固有層中的B細胞合成[60]，與腸上皮細胞表面的分泌成分（secretory component，SC）結(jié)合為SIgA。SIgA與聚合免疫球蛋白受體（polymeric immunoglobulin receptor，pIgR）結(jié)合，經(jīng)轉(zhuǎn)胞吞作用轉(zhuǎn)運至黏液層，促進黏液層清除病原微生物的能力，防止病原微生物的入侵[33, 39]。Sait L C等[71]通過敲除SIgA受體的小鼠模型發(fā)現(xiàn)，由于SIgA受體敲除小鼠腸道產(chǎn)生的IgA無法轉(zhuǎn)運至腸腔，腸系膜淋巴結(jié)培養(yǎng)的細菌數(shù)量上升，血清型IgA和免疫球蛋白G（Immunoglobulin G，IgG）水平升高，表現(xiàn)出腸黏膜屏障功能受損，說明SIgA能夠限制腸道細菌易位，降低腸道細菌入侵引起的全身性免疫反應(yīng)。

2 運動對腸黏膜免疫的影響

多項研究證明，運動過程中機體的血液重新分配，影響腸黏膜屏障免疫穩(wěn)態(tài)。由于腸腔內(nèi)有大量厭氧菌群，固有層中存在豐富的血管和充沛的血液供應(yīng)，腸黏膜從隱窩至絨毛尖端存在急劇變化的氧梯度，形成生理性低氧（physiological hypoxia）[25]；運動可引起腸黏膜血流灌注減少和代謝變化，導(dǎo)致腸道氧分壓（partial pressure of oxygen，PO2）下降。通過多普勒超聲監(jiān)測到，中等強度運動導(dǎo)致腸道血流量下降43％[67]；采用黏膜二氧化碳張力計（Tonometry）測定運動員功率自行車運動時胃腸道二氧化碳分壓（partial pressure of carbon dioxide，PCO2）發(fā)現(xiàn)，運動員胃腸道中PCO2隨著運動強度的增大顯著升高，在進行最大強度運動時均出現(xiàn)胃-動脈和空腸-動脈的PCO2梯度增加、胃和空腸缺血的現(xiàn)象[86]。

本文將從中小強度和大強度兩個方面闡述運動對腸黏膜屏障免疫穩(wěn)態(tài)的影響。

2.1 中小強度運動對腸黏膜屏障免疫穩(wěn)態(tài)的影響

中小強度運動可適度增強腸黏膜屏障的免疫機能，抵御病原微生物入侵。在動物實驗中，評價腸黏膜屏障功能主要通過檢測腸組織形態(tài)結(jié)構(gòu)、SIgA和腸免疫機能相關(guān)的細胞因子水平。研究發(fā)現(xiàn)，中等強度跑臺運動使小鼠腸黏膜增厚，而黏液素分泌未受影響[62]。8周齡雄性Balb/c小鼠進行18周中等強度游泳運動后，與安靜對照小鼠相比，同時都進行5.5 h一次性大強度游泳運動后，中等強度訓(xùn)練小鼠小腸近端SIgA和pIgR水平較高，小腸遠端SIgA和漿細胞IgA+水平較高，TNF-α和IFN-γ mRNA表達較低[30]。Campos-Rodriguez R等[10]通過小鼠傷寒模型發(fā)現(xiàn)，中等強度游泳運動通過增加腸道SIgA水平，減少侵入的傷寒桿菌，降低細菌感染的炎癥病灶數(shù)量。中等強度游泳運動還能夠升高小鼠十二指腸和遠端回腸中α鏈、J鏈及pIgR的mRNA水平和蛋白水平，并能降低腸道固有層中淋巴細胞的數(shù)量，增加小腸白細胞介素（interleukin，IL）-4、IL-6、IL-10、IL-12、TNF-α、TGF-β的mRNA和蛋白水平[97]。此外，研究還發(fā)現(xiàn)，中等強度游泳運動對大鼠腸道屏障緊密連接相關(guān)基因表達的影響有區(qū)域性差異，如顯著上調(diào)十二指腸中表達，并下調(diào)結(jié)腸中這些基因的表達[85]。與此同時，小鼠炎癥性腸病模型的中小強度運動干預(yù)研究中，存在一些相悖的結(jié)論。Saxena A等[72]發(fā)現(xiàn)，為期4周的中等強度跑臺運動干預(yù)降低了小鼠結(jié)腸中促炎細胞因子IL-6、TNF-α和IL-1β水平，減輕了腸道炎癥反應(yīng)，同時上調(diào)趨化因子CCL6的mRNA表達，促進DC和巨噬細胞向炎癥部位的遷移。但是，Cook M D等[17]通過對結(jié)腸炎小鼠進行6周中等強度跑臺運動研究發(fā)現(xiàn)，運動后結(jié)腸IL-1β、IL-6、IL-10、IL-17、TNF-α以及CXCL1 mRNA表達水平升高，表明跑臺運動加重了腸道炎癥反應(yīng)。這種差異可能與建模手段、運動干預(yù)劑量或者小鼠品系等相關(guān)。

由于腸道炎癥反應(yīng)的發(fā)生發(fā)展與腸神經(jīng)活動及心理應(yīng)激密切相關(guān)[3,11]，自主運動和強迫運動干預(yù)可能起到截然不同的效果。在Packer N等[64]研究中，為期4個月自由轉(zhuǎn)輪運動降低小鼠腸淋巴細胞的TNF-α表達水平，保護腸黏膜屏障功能，同樣，Cook M D等[17]發(fā)現(xiàn)，30天自由轉(zhuǎn)輪運動干預(yù)，下調(diào)結(jié)腸中IL-1β、IL-6、IL-10、IL-17、TNF-α以及CXCL1 mRNA表達水平。Allen J等[4]將運動或安靜小鼠的腸道菌群分別移植入無菌（germ-free，GF）小鼠模型，結(jié)果顯示，運動組和安靜組小鼠的腸道菌群存在較大差異，6周自由轉(zhuǎn)輪運動增加腸道菌群豐度（community richness），并在將運動訓(xùn)練或安靜小鼠的腸道菌群分別移植到無菌小鼠后，進一步誘導(dǎo)小鼠急性結(jié)腸炎，結(jié)果顯示，接受運動組小鼠菌群的受體小鼠結(jié)腸中炎性細胞浸潤程度以及IL-1β、IL-23、IDO1和TGF-β的mRNA水平更低，即運動引起腸道菌群的改變可減輕腸道炎癥反應(yīng)。

連蛋白（zonulin）是可調(diào)節(jié)緊密連接、可逆調(diào)控腸通透性的蛋白，在病原微生物的刺激下，zonulin在腸腔中與受體結(jié)合發(fā)生信號轉(zhuǎn)導(dǎo)，使腸道緊密連接開放，腸通透性增加[21,22]。乳果糖（lactulose）是一種異構(gòu)化乳糖，口服后在腸道內(nèi)幾乎不被吸收，僅可能通過緊密連接進入血液循環(huán)；鼠李糖（rhamnose）是單糖，可直接通過腸上皮細胞被吸收。乳果糖和鼠李糖溶液可作為口服探針聯(lián)合使用[65]。腸脂肪酸結(jié)合蛋白（Intestinal fatty acid binding protein，I-FABP）是參與長鏈脂肪酸從腸腔吸收和轉(zhuǎn)運的蛋白，存在于腸上皮細胞中。當腸黏膜屏障損傷時，I-FABP在小腸絨毛中表達并迅速通過損傷的細胞膜，進入血液，在血漿中含量迅速升高。因此，可將I-FABP作為腸黏膜屏障損傷早期的標志物[27]。在人體實驗中，通常根據(jù)血漿或尿液中zonulin含量、乳果糖/鼠李糖（L/R）比值或I-FABP含量評估腸道的通透性。研究發(fā)現(xiàn)，長期中小強度訓(xùn)練可緩解一次大強度運動導(dǎo)致的腸黏膜屏障穩(wěn)態(tài)變化及炎癥反應(yīng)。一次90 min的大強度遞增負荷自行車運動后，運動員糞便中zonulin表達水平低于未訓(xùn)練受試者，說明規(guī)律中小強度訓(xùn)練通過調(diào)節(jié)zonulin表達，緩解大強度運動導(dǎo)致的腸道通透性增加[48,49]。研究發(fā)現(xiàn)，中等強度運動后血漿L/R比值無明顯變化，血漿I-FABP2未升高，證明中等強度運動不會使腸黏膜屏障通透性升高[38]。

因此，目前的研究普遍認為，中小強度運動通過緊密連接蛋白改善腸黏膜屏障通透性，同時改變腸道菌群的組成，并通過上調(diào)SIgA、下調(diào)促炎細胞因子等維持腸黏膜免疫的穩(wěn)態(tài)（圖3）。

2.2 大強度運動對腸黏膜免疫穩(wěn)態(tài)的影響

圖3 運動對腸黏膜屏障免疫穩(wěn)態(tài)的影響

Figure3. Effect of Exercise on Intestinal Barrier and Mucosal Immunity Homeostasis

由以上的研究報道可以看出，大強度運動致腸黏膜缺血、缺氧程度加重，引起腸黏膜屏障功能受損，促進促炎細胞因子分泌和腸道炎癥反應(yīng)，導(dǎo)致機體運動免疫機能失衡（圖3）。

2.3 HIF在運動對腸黏膜免疫穩(wěn)態(tài)影響中的作用機制

HIF是在低氧環(huán)境中調(diào)節(jié)細胞內(nèi)氧穩(wěn)態(tài)的關(guān)鍵轉(zhuǎn)錄因子[37,41,73]，轉(zhuǎn)錄介導(dǎo)缺氧相關(guān)信號途徑。HIF蛋白主要由α和β亞基構(gòu)成，β亞基在組織中穩(wěn)定表達，不受氧分壓變化的影響[74]，α亞基在常氧環(huán)境中經(jīng)脯氨酰羥化酶（prolyl hydroxylase, PHD）[41]羥化其脯氨酸殘基，進而經(jīng)泛素/蛋白酶體途徑降解。當氧分壓降低時，PHD活性被抑制，HIF-1α羥基化修飾水平降低，HIF-1α和HIF-1β結(jié)合，進入胞核，與低氧反應(yīng)元件（hypoxia response elements，HRE）結(jié)合，啟動一系列靶基因的轉(zhuǎn)錄調(diào)控[79]。HIF在腸黏膜中表達，在常氧條件下可被激活，HIF-1α、HIF-2α和HIF-3α3種主要的HIF亞型均存在于腸中[55]，在組織缺氧之前能夠快速啟動炎癥反應(yīng)。

正常情況下，腸黏膜免疫系統(tǒng)時刻接受大量微生物性抗原及食物抗原等的刺激，持續(xù)發(fā)生免疫應(yīng)答和免疫耐受等免疫反應(yīng)，呈現(xiàn)低度生理性炎癥（physiological inflammation）[24]。運動引起腸道局部缺血，導(dǎo)致運動中腹痛、腹瀉和胃腸道出血的發(fā)生，其發(fā)生機制可能與HIF密切相關(guān)。當腸黏膜受損，局部炎癥反應(yīng)加重，一方面，炎癥部位代謝增強，需要合成酶與細胞因子，導(dǎo)致氧需求增加；另一方面，炎癥部位血管功能障礙、血液灌注減少，不能維持免疫細胞浸潤的黏膜組織充足的氧供應(yīng)，使腸黏膜屏障持續(xù)處于低氧水平，活化的中性粒細胞在呼吸爆發(fā)過程中消耗更多氧[9]，可能使缺氧影響到包括腸黏膜下層等更大范圍的組織。

HIF信號途徑對腸黏膜屏障結(jié)構(gòu)完整性有重要作用。HIF-1α可通過誘導(dǎo)MUC3和腸三葉因子（intestinal trefoil factor）等腸道屏障保護基因的轉(zhuǎn)錄[28,52]，形成保護性黏液層。在Karhausen J等[42]的研究中，腸黏膜Hif1a突變，引起小鼠死亡率上升、體重減輕和結(jié)腸長度降低。敲除腸上皮細胞的HIF可顯著降低緊密連接蛋白claudin-1[70]和Defb1等一系列抗菌肽基因[44]的表達水平，引起杯狀細胞的結(jié)構(gòu)異常，改變杯狀細胞分泌的黏液素表達[99]。

同時，HIF也參與免疫細胞的激活和細胞因子的分泌，調(diào)控腸黏膜免疫穩(wěn)態(tài)。在Campbell E L等[9]的研究中，穩(wěn)定結(jié)腸炎小鼠腸黏膜中HIF-1α的表達，可防止細菌與腸上皮接觸，抑制腸黏膜屏障通透性增加，降低IL-1β、IFN-γ和IL-12的分泌，促進IL-6和IL-10的分泌，有效緩解炎癥反應(yīng)。最近的研究表明，小鼠B細胞特異性敲除Hif1a可降低B細胞分泌抗炎細胞因子IL-10，導(dǎo)致炎癥反應(yīng)加重[59]。

由此可見，運動導(dǎo)致機體血液重新分配，內(nèi)臟血液灌流減少，腸道中缺氧程度加劇，誘導(dǎo)HIF-1α穩(wěn)定表達，在這一過程中，HIF-1α對腸黏膜屏障有調(diào)節(jié)作用。中小強度運動中，HIF-1α可能通過調(diào)節(jié)腸黏膜屏障緊密連接，避免腸黏膜屏障通透性增加；而大強度運動導(dǎo)致腸黏膜屏障結(jié)構(gòu)受損后，HIF-1α可能通過參與免疫細胞的激活，啟動炎癥反應(yīng)相關(guān)通路，調(diào)節(jié)細胞因子的分泌，緩解腸黏膜屏障通透性增加，減輕炎癥反應(yīng)。

3 小結(jié)與展望

腸黏膜免疫系統(tǒng)是全身免疫系統(tǒng)的重要組成部分，腸黏膜屏障直接與外界抗原接觸，是機體抵抗病原微生物入侵機體的主要途徑。隨著運動強度增加，內(nèi)臟血流量急劇下降，腸黏膜缺氧程度加劇。大強度運動可能造成腸黏膜免疫穩(wěn)態(tài)被打破，腸道屏障通透性增加，病原微生物入侵，啟動炎癥反應(yīng)；中小強度運動對腸道屏障通透性和腸黏膜免疫穩(wěn)態(tài)可能有改善作用，這些現(xiàn)象與運動過程中HIF-1α表達的上調(diào)有著密切聯(lián)系。中小強度運動中，腸道HIF穩(wěn)定表達可改善腸道屏障通透性；大強度運動后，腸道HIF穩(wěn)定表達可避免腸道屏障組織結(jié)構(gòu)與黏膜免疫功能的進一步破壞。

然而，在不同強度運動中，HIF-1α對腸黏膜屏障的具體作用機制仍不明確，在今后的研究中，需要通過合適的運動模型，闡明不同強度運動與腸道屏障中HIF-1α上調(diào)幅度的關(guān)系，運動過程中HIF介導(dǎo)的信號途徑對腸黏膜屏障代謝的影響，運動后HIF-1α對腸黏膜免疫穩(wěn)態(tài)的維持和保護作用是否具有時效性和適應(yīng)性等問題。這些新的研究成果將為合理的運動訓(xùn)練保護和改善腸黏膜屏障免疫功能的新思路和方法提供強有力的理論與實驗依據(jù)，為運動免疫研究領(lǐng)域提供重要的研究方向。

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Effect of Exercise on Intestinal Barrier Function and Mucosal Immunity Homeostasis

WU Die, CHEN Pei-jie, LUO Bei-bei

Shanghai University of Sport, Shanghai 200438, China.

Intestinal barrier and mucosal immunity homeostasis are the vital defense against pathogen invasion. Exercise induces tissue blood flow redistribution, leading to hypoxia in gastrointestinal tract. Under hypoxic condition, hypoxia-inducible transcription factor (HIF)-1α is phosphorylated and stabilized, regulating intestinal mucosal immune homeostasis. Related studies have revealed that moderate exercise maintains mucosal immunity homeostasis, while heavy exercise causes intestinal barrier dysfunction. Therefore, we briefly introduce the intestinal barrier structure and mucosal immune system; review the effects of different intensities of exercise on intestinal barrier function and mucosal immunity homeostasis; further discuss the possible protective mechanism of HIF-1α. This review provides a new insight for exercise training, intestinal barrier function and mucosal immunity related research areas.

G804.5

A

1000-0000(2018)06-0067-09

10.16469/j.css.201806008

2017-12-30；

2018-05-02

國家自然科學(xué)基金資助項目(31471135); 上海市教委晨光計劃(16CG57); 上海市科委揚帆計劃(17YF1418000);運動健身科技省部共建教育部重點實驗室。

吳嵽,女,在讀博士研究生,主要研究方向為運動免疫學(xué), E-mail:dale_wo@163.com; 陳佩杰,男,教授,博士,博士研究生導(dǎo)師,主要研究方向為運動免疫學(xué)與青少年體質(zhì),E-mail: chenpeijie@sus.edu.cn; 羅貝貝,女,講師,博士,碩士研究生導(dǎo)師,主要研究方向為運動對消化系統(tǒng)的影響,E-mail:lbb0220@126.com。