循環(huán)miRNA生物標(biāo)記物的運(yùn)動(dòng)生理研究進(jìn)展

陳淑婷,晁天樂,劉文萍

循環(huán)miRNA生物標(biāo)記物的運(yùn)動(dòng)生理研究進(jìn)展

陳淑婷1,晁天樂2,劉文萍3

1. 山東農(nóng)業(yè)大學(xué)體育學(xué)院, 山東 泰安 271018 2. 山東農(nóng)業(yè)大學(xué)動(dòng)物科技學(xué)院, 山東 泰安 271018 3. 泰安市精神病醫(yī)院, 山東 泰安 271018

運(yùn)動(dòng)是維持健康和預(yù)防疾病的最佳方法之一，而miRNA被認(rèn)為是運(yùn)動(dòng)后體增益相關(guān)分子機(jī)制的關(guān)鍵調(diào)控因子。循環(huán)miRNA因其穩(wěn)定性、分布廣泛性、以及易檢測(cè)性，特別有望成為未來的運(yùn)動(dòng)相關(guān)非侵入性生物標(biāo)記物?；谘h(huán)miRNA的優(yōu)點(diǎn)，構(gòu)建比目前更易用、更精準(zhǔn)的運(yùn)動(dòng)效果、運(yùn)動(dòng)能力評(píng)估方法，將積極影響當(dāng)前的運(yùn)動(dòng)評(píng)估方法，并更好地監(jiān)測(cè)運(yùn)動(dòng)反應(yīng)。這篇綜述總結(jié)了循環(huán)miRNA的當(dāng)前知識(shí)，與運(yùn)動(dòng)有關(guān)的循環(huán)miRNA的最新研究進(jìn)展，并論述了它們作為運(yùn)動(dòng)相關(guān)生物標(biāo)記物的作用和前景。

循環(huán)miRNA; 運(yùn)動(dòng)生理; 生物標(biāo)記物

生物標(biāo)記物是對(duì)正常生物學(xué)過程、致病過程或?qū)χ委煾深A(yù)的藥理反應(yīng)的客觀測(cè)量和評(píng)估指標(biāo)，可以提供生物體當(dāng)前生理狀態(tài)的準(zhǔn)確信息[1]。臨床表型測(cè)定、代謝產(chǎn)物和蛋白質(zhì)是生物標(biāo)記物主要來源[2]。近年來，循環(huán)miRNA越來越多的被推薦作為診斷和預(yù)后不同生理、病理狀態(tài)的生物標(biāo)記物，如糖尿病[3]，肌肉損傷[4]和癌癥[5,6]。

miRNA是短序列的非編碼調(diào)控RNA，主要通過轉(zhuǎn)錄后負(fù)調(diào)控發(fā)揮功能，在廣泛的細(xì)胞過程中起重要調(diào)節(jié)作用。運(yùn)動(dòng)訓(xùn)練有助于維持和改善健康，是許多疾病的有效非藥物治療方法[7]。早在2007年[8]和2011年[9]就有報(bào)道，miRNA能響應(yīng)運(yùn)動(dòng)訓(xùn)練發(fā)生變化。從那時(shí)起，關(guān)于運(yùn)動(dòng)與miRNA之間關(guān)聯(lián)的研究不斷開展。這些研究表明，miRNA參與肌肉的發(fā)育、恢復(fù)和損傷，并與有氧運(yùn)動(dòng)能力直接相關(guān)。短期或長期運(yùn)動(dòng)會(huì)大幅改變肌肉和循環(huán)系統(tǒng)中miRNA的表達(dá)量。其中，循環(huán)系統(tǒng)miRNA因其分布特點(diǎn)和穩(wěn)定性，成為了運(yùn)動(dòng)相關(guān)非侵入性生物標(biāo)記物的候選分子[10,11]。但是，由于運(yùn)動(dòng)的復(fù)雜性及干擾因素的多樣性，至今對(duì)于循環(huán)miRNA與運(yùn)動(dòng)間的具體關(guān)系所知甚少。此外，由于miRNA作用多樣，很難理解不同生理狀態(tài)下miRNA表達(dá)譜變化的實(shí)際意義。不同研究間的miRNA檢測(cè)結(jié)果往往存在矛盾，這可能是研究的試驗(yàn)?zāi)Ｐ?、運(yùn)動(dòng)條件、樣品來源或分析方法差異等因素造成的。盡管如此，仍有跡象表明miRNA與特定運(yùn)動(dòng)類型能夠?qū)?yīng)，這增強(qiáng)了miRNA可用作運(yùn)動(dòng)相關(guān)生物標(biāo)記物的可能性。本綜述旨在總結(jié)運(yùn)動(dòng)相關(guān)循環(huán)miRNA的最新研究進(jìn)展，探討循環(huán)miRNA作為運(yùn)動(dòng)相關(guān)生物標(biāo)記物的作用和面臨的問題。

1 運(yùn)動(dòng)與miRNA

1.1 運(yùn)動(dòng)與健康

眾所周知，堅(jiān)持運(yùn)動(dòng)對(duì)維持心血管健康，提高認(rèn)知和免疫功能，改善能量代謝均起到極大積極作用，也是改善生活質(zhì)量的最好且最有效的方法之一[12]。定期運(yùn)動(dòng)可降低50％心血管疾病患病風(fēng)險(xiǎn)、29％癌癥死亡率，以及52％的全因死亡率[13,14]。長期參與體育運(yùn)動(dòng)不但可改善生活質(zhì)量，還能降低抑郁癥和腎臟疾病風(fēng)險(xiǎn)[15-17]。由于體育運(yùn)動(dòng)能大幅提高人體健康，堅(jiān)持運(yùn)動(dòng)還等于節(jié)省了醫(yī)療保健開支[18]。根據(jù)類型、強(qiáng)度和頻率不同，運(yùn)動(dòng)可引發(fā)身體的急性或慢性變化，有氧/阻力運(yùn)動(dòng)、急性/慢性運(yùn)動(dòng)引起的生理變化各不相同[19]。在肌肉纖維中，運(yùn)動(dòng)通過機(jī)械刺激和代謝激活等途徑調(diào)節(jié)蛋白編碼基因和非編碼基因的表達(dá)，其中包括miRNA[2,20]。

1.2 miRNA的生物學(xué)功能

當(dāng)前在人類基因組中，有2600多條miRNA獲得正式命名。MicroRNAs是小分子的內(nèi)源性非編碼RNA，廣泛參與基因轉(zhuǎn)錄后調(diào)控[21]。編碼miRNA的基因通過RNA聚合酶II或III激活，轉(zhuǎn)錄到細(xì)胞核中，并通過一系列復(fù)雜生物學(xué)發(fā)生過程形成[22]。

在基因表達(dá)轉(zhuǎn)錄后調(diào)控中，miRNA能夠通過靶向mRNA的3'-非翻譯區(qū)或其他區(qū)域發(fā)生針對(duì)性結(jié)合[23]。如果靶標(biāo)區(qū)域完全互補(bǔ)，則蛋白Ago2可以裂解靶標(biāo)mRNA分子，致其降解；在部分靶向互補(bǔ)情況下，相互作用往往為翻譯抑制[24]。因此，miRNA實(shí)際作用為引發(fā)靶標(biāo)mRNA降解或翻譯抑制，或兩種過程組合發(fā)生[25]。

1.3 miRNA與運(yùn)動(dòng)

在已命名miRNA中，很大一部分被報(bào)道能通過多種生物學(xué)途徑對(duì)各種細(xì)胞過程（包括發(fā)育、增殖和凋亡）起調(diào)節(jié)作用[25,26]。當(dāng)前，越來越多的miRNA被發(fā)現(xiàn)參與肌肉發(fā)育調(diào)控，同時(shí)這些miRNA的表達(dá)受運(yùn)動(dòng)的調(diào)節(jié)。如miR-1，miR-133和miR-206三種miRNA在人體肌肉組織中高表達(dá)，且其表達(dá)受到運(yùn)動(dòng)的影響[27]。

在運(yùn)動(dòng)生理活動(dòng)中，miRNA能夠以組織特異性或時(shí)間特異性模式釋放到體循環(huán)中，而機(jī)體中普遍的免疫反應(yīng)以及活動(dòng)中骨骼肌和心肌組織的適應(yīng)性調(diào)節(jié)進(jìn)一步影響了這種反應(yīng)[28]。近年來，有多項(xiàng)研究指出，體循環(huán)中miRNA表達(dá)譜的改變可以作為某些生理適應(yīng)或病理變化的分子標(biāo)記[29-31]。

2 循環(huán)miRNA作為生物標(biāo)記物的有利特征

2.1 循環(huán)miRNA的生成途徑

近年來發(fā)現(xiàn)，在血清、血漿、唾液、尿液、乳汁中穩(wěn)定存在大量miRNA[32-35]，這些miRNA被稱作循環(huán)miRNA（circulating miRNA，ci-miRNA）。根據(jù)來源，可將循環(huán)miRNA分為三類：（一）遭受損傷、慢性炎癥、細(xì)胞凋亡的細(xì)胞、或半衰期短的細(xì)胞（如血小板）發(fā)生被動(dòng)泄漏產(chǎn)生的循環(huán)miRNA；（二）通過細(xì)胞衍生膜囊泡（如微粒，外泌體，脫落的囊泡和凋亡小體）主動(dòng)分泌的循環(huán)miRNA；（三）通過蛋白質(zhì)-miRNA復(fù)合物主動(dòng)分泌產(chǎn)生的循環(huán)miRNA[31,36,37]。以上三種途徑產(chǎn)生的miRNA均可進(jìn)入循環(huán)系統(tǒng)或體液，并在運(yùn)輸至受體細(xì)胞位置后被吸收，吸收方式可以為內(nèi)吞、膜融合或者配體-受體結(jié)合等多種方式[36]。

2.2 循環(huán)miRNA的穩(wěn)定性

循環(huán)miRNA穩(wěn)定性較高，其原因是：（1）部分循環(huán)miRNA被囊泡包裹，如外泌體或凋亡小體，避免了與核糖核酸酶的接觸[38]；（2）miRNA本身分子較小及特殊結(jié)構(gòu)帶來抗降解能力；（3）miRNA與蛋白質(zhì)、核磷脂或高密度脂蛋白形成復(fù)合物提高了自身抗降解能力[38-40]。目前認(rèn)為miRNA穩(wěn)定性主要源自其對(duì)核糖核酸酶作用的抗性[41-43]，這種穩(wěn)定性意味著miRNA在各種體液中具備較長壽命，因此有成為標(biāo)記物的潛力[31,40,44]。此外，由于循環(huán)miRNA可通過血液或其他體液采集，使得其在針對(duì)活體、尤其是人體的研究中應(yīng)用更為簡便，這也表明它們是生物標(biāo)記物的理想來源[45]。內(nèi)源性循環(huán)miRNA對(duì)嚴(yán)酷脅迫（如高溫，反復(fù)凍融循環(huán)）、pH值過低或過高，和長存儲(chǔ)時(shí)間等條件均有高抗性[40,46,47]，但游離循環(huán)miRNA相對(duì)穩(wěn)定性弱于囊泡和復(fù)合體循環(huán)miRNA[30]。此外，已進(jìn)行穩(wěn)定性測(cè)試的miRNA數(shù)量相當(dāng)有限，是否所有miRNA均能在循環(huán)狀態(tài)下保持高穩(wěn)定性仍為未知[48]。綜上而言，至少一部分循環(huán)miRNA已被發(fā)現(xiàn)具備較好的穩(wěn)定性，符合生物標(biāo)記物基本要求。

2.3 循環(huán)miRNA的易采集性

循環(huán)miRNA能夠通過無創(chuàng)或微創(chuàng)方法進(jìn)行樣品收集[49-51]，這一特征使循環(huán)miRNA具備以下優(yōu)點(diǎn)：（1）避免了其他標(biāo)記物樣品可能涉及的侵入性手術(shù)；（2）為某些不能采集組織的重要器官（如心?。?，提供了信息采集的可能；（3）避免了目標(biāo)組織太小或難以取得帶來的采樣限制[31,52]。

循環(huán)miRNA的便捷性使其能夠替代部分目前繁瑣昂貴的檢測(cè)方法，如X射線、計(jì)算機(jī)斷層掃描（CT）、正電子發(fā)射斷層掃描（PET）-CT、磁共振成像、超聲檢查等[31,53]。而根據(jù)目前病理學(xué)方面的研究結(jié)果，循環(huán)miRNA作為生物標(biāo)記物的特異性和靈敏度相對(duì)較高。例如，循環(huán)miRNA表達(dá)量變化能夠區(qū)分乍看相似，卻需要不同治療方案的疾病[31,53]。

如上所述，miRNA存在于幾乎所有體液，完全滿足生物標(biāo)記物的相對(duì)可及性和最小侵入性原則。然而，與體組織相比，循環(huán)系統(tǒng)中的miRNA整體表達(dá)量偏低，因此循環(huán)miRNA的實(shí)際應(yīng)用仍有許多問題需要注意[54]。

3 與運(yùn)動(dòng)相關(guān)的循環(huán)miRNA

在運(yùn)動(dòng)引起的轉(zhuǎn)錄后水平分子調(diào)控過程中，循環(huán)miRNA被認(rèn)為是重要的調(diào)控因子。多種miRNA已被確認(rèn)在肌肉或心臟中特異性表達(dá)，可參與調(diào)節(jié)肌肉生長發(fā)育、代謝適應(yīng)、肌肉損傷修復(fù)等生物學(xué)過程。健康狀態(tài)下，這些miRNA在循環(huán)系統(tǒng)中表達(dá)量極低。因此，可通過檢測(cè)表達(dá)量來將它們用作生物標(biāo)記以測(cè)試特定運(yùn)動(dòng)方案效果或及早發(fā)現(xiàn)被測(cè)者對(duì)高運(yùn)動(dòng)量的異常反應(yīng)（如心肌梗塞）[8,55,56]。

根據(jù)被測(cè)者、鍛煉類型、持續(xù)時(shí)間和強(qiáng)度的不同，發(fā)生上調(diào)和下調(diào)的循環(huán)miRNA也會(huì)發(fā)生相應(yīng)的變化[10,57]。例如，在急性耐力訓(xùn)練后，血清中miR-21、miR-221、miR-222和miR-146a的表達(dá)水平被發(fā)現(xiàn)瞬時(shí)升高，進(jìn)一步分析發(fā)現(xiàn)它們主要與炎癥、缺氧、血管生成和肌肉分化等生物學(xué)途徑有關(guān)[9]。而其它研究中，在相同類型的鍛煉后，miR-146a和miR-221的血清表達(dá)水平卻非常低[58,59]。

miR-486在骨骼肌和心肌組織高表達(dá)，以70％最大攝氧量進(jìn)行60 min穩(wěn)態(tài)自行車運(yùn)動(dòng)后，發(fā)現(xiàn)miR-486表達(dá)量顯著下降，且在24 h內(nèi)恢復(fù)到基線水平。該研究也發(fā)現(xiàn)循環(huán)miR-486的變化率與最大攝氧量顯著相關(guān)，表明循環(huán)系統(tǒng)miR-486表達(dá)量可能是有氧運(yùn)動(dòng)能力的生物標(biāo)記物[58]。

循環(huán)系統(tǒng)中miR-1、miR-133a、miR-206、miR-208a和miR-499被發(fā)現(xiàn)在馬拉松比賽后顯著增加，且這些miRNA被證明與肌肉分化增殖有關(guān)。有觀點(diǎn)認(rèn)為，這種循環(huán)miRNA表達(dá)量增加是由于組織破壞和細(xì)胞凋亡引起的，或是由于骨骼肌細(xì)胞持續(xù)收縮，導(dǎo)致細(xì)胞內(nèi)miRNA代謝和分泌增強(qiáng)引發(fā)的[60;61]。然而在同一項(xiàng)研究中，65％最大攝氧量下運(yùn)動(dòng)1 h未能影響循環(huán)miRNA表達(dá)水平，但這項(xiàng)研究還是發(fā)現(xiàn)循環(huán)miR-1，miR-133a，miR-206與運(yùn)動(dòng)員的有氧運(yùn)動(dòng)能力之間的相關(guān)性，并推斷出它們作為有氧運(yùn)動(dòng)能力生物標(biāo)記物的價(jià)值[60]。

近幾年，循環(huán)miRNA在運(yùn)動(dòng)生理中的實(shí)際功能逐漸揭示。大鼠和人類志愿者運(yùn)動(dòng)試驗(yàn)表明，外泌體循環(huán)miRNA miR-342-5p是重要的心肌保護(hù)分子。miR-342-5p被發(fā)現(xiàn)能夠通過靶向Caspase 9和Jnk2抑制缺氧、復(fù)氧誘導(dǎo)的心肌細(xì)胞凋亡，還通過靶向磷酸酶基因Ppm1f增強(qiáng)了細(xì)胞生存率，并在人體內(nèi)源性心肌保護(hù)機(jī)制中起關(guān)鍵作用[62]?？偟膩砜?，循環(huán)miRNA在運(yùn)動(dòng)生理中確有實(shí)際調(diào)控作用，具有很高的生物標(biāo)記物價(jià)值，但仍有待更加廣泛和徹底的研究理解。

4 循環(huán)miRNA實(shí)際應(yīng)用中的問題

4.1 試驗(yàn)設(shè)計(jì)

在運(yùn)動(dòng)生理學(xué)和運(yùn)動(dòng)醫(yī)學(xué)中，試驗(yàn)設(shè)計(jì)對(duì)影響因素的錯(cuò)估或忽視往往是造成結(jié)果謬誤的主要原因，而循環(huán)miRNA的研究應(yīng)用也必須注意這一問題[63-65]。運(yùn)動(dòng)量的差異、被測(cè)者運(yùn)動(dòng)能力、被測(cè)者運(yùn)動(dòng)適應(yīng)性、運(yùn)動(dòng)前或運(yùn)動(dòng)中飲食飲水等因素均可能影響分析結(jié)果[66,67]。

血樣采集本身也是引入變異的原因之一。采集血樣時(shí)的肌肉狀態(tài)與多種物質(zhì)含量相關(guān)[68]。采集血樣時(shí)，使用止血帶輔助采集會(huì)引起靜脈淤滯，進(jìn)而導(dǎo)致穿刺部位血液分析物濃度增加[69]。此外，其他常見誤差源有：樣品基質(zhì)、抽血與樣品處理之間的時(shí)間、樣品存儲(chǔ)時(shí)間、樣品存儲(chǔ)溫度等[70-74]。在多因素影響的外界環(huán)境下和機(jī)體內(nèi)不穩(wěn)定的生化環(huán)境下，循環(huán)miRNA的準(zhǔn)確測(cè)量頗為困難[30]。

目前，在不同類型循環(huán)miRNA中，最常用的當(dāng)屬血清miRNA。但采血、運(yùn)輸和存儲(chǔ)過程可能污染樣品[75]，采血針頭中的少量組織細(xì)胞、或血樣溶血都可導(dǎo)致血清miRNA污染[75,76]。miRNA可以在凝血過程中由血小板釋放，也可從溶血性紅細(xì)胞中釋放出來[76,77]。在后一種情況下，使用miR-23a與miR-451的ΔCT比可用于檢查微溶血事件（如果為N 7則為溶血），進(jìn)而判斷樣品污染程度[78]。

4.2 樣品基質(zhì)與處理方式的選擇

在開發(fā)新型生物標(biāo)記物時(shí)，正確的樣品基質(zhì)至關(guān)重要，其對(duì)最終研究結(jié)果影響極大[79,80]。有報(bào)道稱相同物種個(gè)體之間血清miRNA表達(dá)模式穩(wěn)定，測(cè)定結(jié)果可重復(fù)且一致性較好[32]，其他研究證明血漿來源miRNA也有類似性質(zhì)[33]。

部分抗凝劑對(duì)血樣中miRNA濃度能夠造成影響，因此應(yīng)慎重選擇。肝素和檸檬酸均為常見血液抗凝劑，但它們均能干擾PCR反應(yīng)酶活性，因此在miRNA的qPCR定量中，不建議將這兩種抗凝劑處理過的血樣與其它類型樣品混用[81,82]。與肝素不同，EDTA可從PCR反應(yīng)混合物中去除，因此被認(rèn)為是基于PCR的miRNA分析樣品最佳抗凝劑[83]。NaF/KOx抗凝血漿常被認(rèn)為是EDTA的合適替代品，但可能影響miRNA檢測(cè)結(jié)果[84]。

血樣的離心時(shí)間和離心速度也會(huì)嚴(yán)重影響EDTA血漿樣品中的最終miRNA濃度，因?yàn)樗赡軙?huì)導(dǎo)致血小板衍生的miRNA污染[48]。血清miRNA則對(duì)這種預(yù)處理變異不太敏感[85]。

4.3 循環(huán)miRNA檢測(cè)方法的選擇

目前，測(cè)量循環(huán)miRNA的主要方法是qRT-PCR、芯片檢測(cè)和二代測(cè)序技術(shù)（NGS）。

qRT-PCR技術(shù)可應(yīng)用于各種不同類型RNA分子的定量檢測(cè)與比較，在循環(huán)miRNA檢測(cè)中始終起到重要的作用。miRNA的qRT-PCR檢測(cè)主要有莖環(huán)引物法和多聚腺苷酸尾PCR法[86]。qRT-PCR技術(shù)特異性好、檢測(cè)快、成本低，但亦有試驗(yàn)操作繁瑣、單次檢測(cè)miRNA數(shù)量少等劣勢(shì)。

芯片檢測(cè)也稱微陣列，是檢測(cè)核酸突變和RNA表達(dá)量的常用技術(shù)。核酸芯片基于qPCR或雜交技術(shù)，通過探針一次測(cè)定大量靶RNA的表達(dá)量或堿基突變信息[5,87]。芯片的局限性包括酶標(biāo)記中的序列特異性標(biāo)記偏倚，缺乏絕對(duì)定量能力以及相對(duì)較低的動(dòng)態(tài)范圍。此外，miRNA芯片的另一缺陷是對(duì)探針設(shè)計(jì)的依賴性，無法用于檢測(cè)和發(fā)現(xiàn)新miRNA[5]。

二代測(cè)序技術(shù)具有很高的動(dòng)態(tài)檢測(cè)范圍、靈敏度和可重復(fù)性，在擴(kuò)大檢測(cè)范圍，提高結(jié)果準(zhǔn)確性方面均具有優(yōu)勢(shì)。該技術(shù)既能檢測(cè)已知miRNA，也可以鑒定新型miRNA。二代測(cè)序的局限性主要涉及技術(shù)問題，如酶促連接導(dǎo)致的序列特異性偏倚。值得注意的是，盡管二代測(cè)序技術(shù)成本快速下降，miRNA測(cè)序的價(jià)格卻始終變化不大，因此循環(huán)miRNA的檢測(cè)仍需注意多方法結(jié)合使用。

5 結(jié)語

近年來，循環(huán)miRNA作為運(yùn)動(dòng)相關(guān)生物標(biāo)記物的潛力越來越重要。通過檢測(cè)各種體液中大量存在的循環(huán)miRNA，可實(shí)現(xiàn)對(duì)各種類型運(yùn)動(dòng)適應(yīng)癥狀或運(yùn)動(dòng)能力的快速無創(chuàng)或微創(chuàng)檢測(cè)分析。此外，低成本、易檢測(cè)使循環(huán)miRNA成為運(yùn)動(dòng)相關(guān)分子機(jī)制研究中的潛在生物標(biāo)記。當(dāng)前，循環(huán)miRNA廣泛應(yīng)用的主要障礙是難以保證樣本質(zhì)量和完整性。盡管目前仍有方法學(xué)上的問題存在，但只要正確使用試劑、選擇適合的RNA提取方法、以及避免樣本污染，循環(huán)miRNAs仍可為運(yùn)動(dòng)生理學(xué)的檢測(cè)、診斷和分析提供準(zhǔn)確的信息。總的來說，循環(huán)miRNAs作為運(yùn)動(dòng)相關(guān)生物標(biāo)記物的臨床應(yīng)用潛力極大，但還需通過更多研究來進(jìn)一步驗(yàn)證。

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Research Progress of Circulating miRNA as Biomarker in Exercise Physiology

CHEN Shu-ting1, CHAO Tian-le2, LIU WEN-ping3

1.271018,2.271018,3.271000,

Exercise is one of the best ways to maintain health and prevent disease, and miRNA is considered to be a key regulatory factor related to exercise benefits. Because of its stability, wide distribution and easy detection, circulating miRNA is expected to become a non-invasive exercise related biomarker in the future. Based on the advantages of circulating miRNA, the construction of a more easy-to-use and more accurate method for the evaluation of motor effect and motor ability will positively affect the current method of motor evaluation and better monitor the exercise response. This review summarizes the current knowledge of circulating miRNAs, the latest research progress of miRNAs related to exercise, and discusses their functions and prospects as biomarkers related to exercise.

Circulating miRNA; exercise physiology; biomarker

G804.23

A

1000-2324(2022)01-0163-08

10.3969/j.issn.1000-2324.2022.01.025

2021-02-10

2021-03-21

陳淑婷(1975-),女,碩士,副教授,長期從事高校體育教育與運(yùn)動(dòng)生理學(xué)研究. E-mail:wfdzz@sdau.edu.cn