黃紅云馮世慶陳琳毛更生鄭遵成

·專家論壇·

醫(yī)學(xué)修復(fù)學(xué)
——現(xiàn)代醫(yī)學(xué)重要支撐學(xué)科

黃紅云1馮世慶2陳琳3毛更生1鄭遵成4

隨著醫(yī)學(xué)快速發(fā)展，現(xiàn)已呈現(xiàn)為臨床醫(yī)學(xué)、預(yù)防醫(yī)學(xué)、康復(fù)醫(yī)學(xué)、修復(fù)醫(yī)學(xué)或醫(yī)學(xué)修復(fù)學(xué)四大發(fā)展方向和分支。醫(yī)學(xué)修復(fù)學(xué)作為采用修復(fù)策略治療和預(yù)防人類疾病和損害以及衰老導(dǎo)致的機(jī)體結(jié)構(gòu)和功能障礙的醫(yī)學(xué)學(xué)科體系正在受到醫(yī)學(xué)界越來越多的關(guān)注，尤其是細(xì)胞治療技術(shù)和生物工程技術(shù)正在催化這一學(xué)科體系加快發(fā)展。本文概述其發(fā)展概況、修復(fù)機(jī)制、學(xué)科基本概念和涵蓋范圍、加速推動其發(fā)展的舉措，并提出“醫(yī)學(xué)修復(fù)學(xué)是醫(yī)學(xué)發(fā)展的重要方向，是現(xiàn)代醫(yī)學(xué)學(xué)科體系的四駕馬車之一”。

修復(fù)； 策略； 機(jī)制； 組織療法； 生物技術(shù)

隨著人類社會發(fā)展，醫(yī)學(xué)現(xiàn)已成為自然科學(xué)和社會科學(xué)交匯的最重要學(xué)科之一。醫(yī)學(xué)本身可分為臨床醫(yī)學(xué)、預(yù)防醫(yī)學(xué)、康復(fù)醫(yī)學(xué)、再生醫(yī)學(xué)以及近十幾年的修復(fù)醫(yī)學(xué)或醫(yī)學(xué)修復(fù)學(xué)等不同重點(diǎn)分支和發(fā)展方向；這些分支交叉融合發(fā)展，其核心目的是提高人類的健康水平或延年益壽。醫(yī)學(xué)修復(fù)學(xué)相關(guān)研究、治療和預(yù)防現(xiàn)在已受到越來越多的關(guān)注和重視，本文著重闡述和梳理醫(yī)學(xué)修復(fù)學(xué)的發(fā)展概況和它發(fā)展的必然走向。

一、衰老的基本過程

生物體包括人類的衰老是一個必經(jīng)的自然過程，疾病或外來損害會加速這一衰老或死亡過程。以細(xì)胞為例，任何一種細(xì)胞都有其自身的生命周期，當(dāng)幼稚細(xì)胞或干、祖、前體細(xì)胞分化到功能細(xì)胞或成熟階段時(shí)，其主要使命就是維持自身存活和發(fā)揮其生物功能，與此同時(shí)逐漸開始老化；在這個階段如果受到外因意外損害或體內(nèi)疾病造成內(nèi)環(huán)境不利改變，細(xì)胞耐受性和順應(yīng)性就會降低，細(xì)胞自身的生命周期將縮短。組織、器官、系統(tǒng)和生物體也像細(xì)胞一樣有其自身生命周期，除了自身衰老正常過程外，都有可能受到外因損害或內(nèi)在疾病影響，而縮短其生命周期。

二、醫(yī)學(xué)修復(fù)學(xué)發(fā)展概況

醫(yī)學(xué)修復(fù)學(xué)或修復(fù)醫(yī)學(xué)目前正處在發(fā)展早期，學(xué)科概念尚無統(tǒng)一認(rèn)識和理念，現(xiàn)階段主要有以下兩種觀點(diǎn)。

1.把修復(fù)醫(yī)學(xué)視為臨床醫(yī)療的一種治療策略和方法[1]，它包括四個層次，（1）把蛋白或基因作為藥物輸入機(jī)體，如胰島素、干擾素、生長激素和促紅細(xì)胞生成素等；（2）細(xì)胞移植直接注射病變部位，或組織工程中把細(xì)胞作為種子置于材料形成組織或器官后移植；（3）干細(xì)胞移植；（4）納米或更微小材料移植。

2.把修復(fù)醫(yī)學(xué)視為基于修復(fù)器官功能和組織損傷的跨學(xué)科補(bǔ)充和替代醫(yī)學(xué)（CAM）[2]，治療方法包括營養(yǎng)補(bǔ)充劑、化學(xué)藥物、植物藥物和激素等替代治療（https:// restorativemedicine.org/）。

在深入研究上述兩種觀點(diǎn)后，我們認(rèn)為修復(fù)醫(yī)學(xué)或醫(yī)學(xué)修復(fù)學(xué)不僅僅是醫(yī)療方法，也不只是補(bǔ)充和替代醫(yī)學(xué)，而是一種新的醫(yī)學(xué)學(xué)科體系，這一醫(yī)學(xué)學(xué)科的目的是“采用修復(fù)治療和預(yù)防策略，通過修復(fù)機(jī)制，最大程度恢復(fù)和預(yù)防人類疾病和損害以及衰老導(dǎo)致的機(jī)體結(jié)構(gòu)和功能障礙”。當(dāng)臨床醫(yī)學(xué)對人體各系統(tǒng)采用常規(guī)治療無能為力時(shí)，最終都需要通過修復(fù)機(jī)制和策略來改變和恢復(fù)受損的結(jié)構(gòu)和功能。

以神經(jīng)系統(tǒng)神經(jīng)修復(fù)學(xué)發(fā)展過程為例，在人們過去的認(rèn)知中，神經(jīng)系統(tǒng)疾病、損害和自身衰老導(dǎo)致的結(jié)構(gòu)和功能損害，尤其是損害后遺癥期，被一直認(rèn)為是無法改變的。先驅(qū)者最開始都是以探索改變神經(jīng)結(jié)構(gòu)和功能障礙的方法為主，得到神經(jīng)結(jié)構(gòu)和功能改善的現(xiàn)象，隨后才進(jìn)一步研究神經(jīng)修復(fù)的機(jī)制[3-5]。

由于神經(jīng)修復(fù)涉及多學(xué)科，從研究者自身學(xué)科角度就提出了一些本學(xué)科分支理念或作為一種治療方法，如修復(fù)神經(jīng)病學(xué)、修復(fù)神經(jīng)外科學(xué)、修復(fù)神經(jīng)科學(xué)、外科神經(jīng)修復(fù)學(xué)、神經(jīng)修復(fù)技術(shù)或療法等[6-12]；但這些學(xué)科分支或技術(shù)的名稱都無法涵蓋和整合所有神經(jīng)修復(fù)的內(nèi)涵和外延，最后以神經(jīng)修復(fù)學(xué)學(xué)科的建立才整合了全部與神經(jīng)修復(fù)相交叉學(xué)科的相關(guān)研究內(nèi)涵和外延[13-15]。

鑒于此，用醫(yī)學(xué)修復(fù)學(xué)而不是修復(fù)醫(yī)學(xué)命名這一體系應(yīng)更為合適和準(zhǔn)確，其系列分支可以分別命名為× ×修復(fù)學(xué)學(xué)科，如神經(jīng)修復(fù)學(xué)、口腔修復(fù)學(xué)、腎臟修復(fù)學(xué)等。

三、醫(yī)學(xué)修復(fù)學(xué)的修復(fù)機(jī)制

從修復(fù)機(jī)制上看，醫(yī)學(xué)修復(fù)學(xué)機(jī)制主要有保護(hù)、信號調(diào)控、免疫調(diào)控、結(jié)構(gòu)修復(fù)、替代、再生、促血管新生等，目前經(jīng)修復(fù)治療后只有很少部分的功能恢復(fù)是來自于再生機(jī)制。實(shí)際上再生就如同直角三角形是特殊三角形一樣，它是一種特殊修復(fù)機(jī)制，僅僅是眾多修復(fù)機(jī)制的其中之一，大多數(shù)功能恢復(fù)是來自于再生以外的其他修復(fù)機(jī)制；尤其在細(xì)胞治療異軍突起后，發(fā)現(xiàn)細(xì)胞旁分泌的保護(hù)和信號調(diào)控、免疫調(diào)控、結(jié)構(gòu)修復(fù)、替代、促特殊組織和血管新生等各種修復(fù)機(jī)制作用就更加明顯和突出，修復(fù)的機(jī)制包括再生但比再生更寬泛，用修復(fù)描述功能恢復(fù)的機(jī)制更準(zhǔn)確。

因此從修復(fù)機(jī)制探索發(fā)展歷程上看，再生醫(yī)學(xué)只能是作為一個過渡階段而成為醫(yī)學(xué)修復(fù)學(xué)的一部分，而醫(yī)學(xué)修復(fù)學(xué)涵蓋的所有機(jī)制和治療策略探索必將成為醫(yī)學(xué)發(fā)展研究的重要方向。

四、醫(yī)學(xué)修復(fù)學(xué)學(xué)科基本概念和涵蓋范圍

醫(yī)學(xué)修復(fù)學(xué)是通過修復(fù)策略和機(jī)制來治療和預(yù)防人類疾病和損害以及衰老導(dǎo)致的機(jī)體結(jié)構(gòu)和功能障礙的醫(yī)學(xué)學(xué)科體系。治療和預(yù)防策略包括：細(xì)胞和組織移植、組織工程和生物工程技術(shù)、干預(yù)性修復(fù)手術(shù)、調(diào)控或刺激技術(shù)、藥物（包括營養(yǎng)補(bǔ)充劑，化學(xué)藥物、植物藥物和激素等）、積極心理干預(yù)、補(bǔ)充和替代療法以及其他有價(jià)值技術(shù)和手段。從醫(yī)學(xué)學(xué)科系統(tǒng)基本構(gòu)成來看，醫(yī)學(xué)修復(fù)學(xué)涵蓋范圍或分支應(yīng)包括神經(jīng)修復(fù)學(xué)、心臟修復(fù)學(xué)、血管修復(fù)學(xué)、呼吸修復(fù)學(xué)、消化修復(fù)學(xué)（包括肝臟修復(fù)學(xué)、胰臟修復(fù)學(xué)和胃腸修復(fù)學(xué)）、腎臟修復(fù)學(xué)、骨修復(fù)學(xué)、內(nèi)分泌修復(fù)學(xué)、免疫修復(fù)學(xué)和口腔修復(fù)學(xué)等學(xué)科。

機(jī)體作為生物體是一個完整系統(tǒng)，現(xiàn)代生物學(xué)將其向下分為系統(tǒng)、器官、組織、細(xì)胞、亞細(xì)胞器、分子和電子等不同層面。修復(fù)在不同層面采用不同方法和手段，并具有相應(yīng)修復(fù)機(jī)制；以神經(jīng)修復(fù)學(xué)治療策略和機(jī)制為例[16]：（1）在器官層面上，采用神經(jīng)嫁接、脊髓損傷內(nèi)減壓等方法，作用機(jī)制主要是神經(jīng)結(jié)構(gòu)修復(fù)、神經(jīng)軸突再生、神經(jīng)保護(hù)等；（2）在組織層面上采用細(xì)胞移植、組織工程方法，作用機(jī)制主要是神經(jīng)重塑、突觸重分布、神經(jīng)網(wǎng)絡(luò)重建、神經(jīng)替代、神經(jīng)再生和血管再生等；（3）在細(xì)胞層面上采用細(xì)胞移植、因子和藥物治療等方法，改變局部或整體環(huán)境，促使細(xì)胞結(jié)構(gòu)和功能改變，作用機(jī)制主要是脫髓鞘修復(fù)、軸突再生、突觸重分布、免疫調(diào)控和血管再生等；（4）在細(xì)胞器層面上采用藥物等方法和促進(jìn)自噬基因活性[17]，作用機(jī)制主要是神經(jīng)保護(hù)、抗氧化、膜穩(wěn)定與保護(hù)、清除損傷線粒體等；（5）在分子層面上采用基因轉(zhuǎn)染或修飾、基因修復(fù)、重編程等生物工程技術(shù)、細(xì)胞治療調(diào)節(jié)微環(huán)境改變分子結(jié)構(gòu)和功能，其作用機(jī)制主要是神經(jīng)調(diào)控、神經(jīng)保護(hù)、免疫調(diào)控等；（6）在電子水平上采用細(xì)胞移植、電極植入等調(diào)控電信號，主要作用機(jī)制是神經(jīng)調(diào)控、神經(jīng)刺激或激活、腦機(jī)對話等；（7）未來可能在量子水平上會有相應(yīng)方法和修復(fù)機(jī)制。

如同神經(jīng)修復(fù)學(xué)的整體神經(jīng)修復(fù)過程理論和神經(jīng)修復(fù)法則一樣[16]，在生理情況下生物體通過自身完整修復(fù)系統(tǒng)來對抗和抵御外來損害、疾病和自身衰老的致?lián)p因素，但當(dāng)致?lián)p因素大到自身無法對抗和抵御時(shí)，就會處于結(jié)構(gòu)和功能障礙等病理和病理生理的失衡狀態(tài)，此時(shí)就需要采用人為的外來干預(yù)策略，才能維持或逆轉(zhuǎn)被損害的結(jié)構(gòu)和功能；這種通過自體或人為干預(yù)的不同修復(fù)機(jī)制維持和修復(fù)病理和病理生理狀態(tài)結(jié)構(gòu)和功能完整性的規(guī)律和定律可稱為“整體醫(yī)學(xué)修復(fù)過程理論和醫(yī)學(xué)修復(fù)法則”。

五、加速推動醫(yī)學(xué)修復(fù)學(xué)發(fā)展的舉措

細(xì)胞治療、生物工程和組織工程以及調(diào)控技術(shù)的研治進(jìn)展，推動了醫(yī)學(xué)修復(fù)學(xué)快速發(fā)展，尤其在細(xì)胞治療技術(shù)和生物工程技術(shù)異軍突起后，正在催化這一學(xué)科體系加快發(fā)展。以神經(jīng)修復(fù)學(xué)為例，細(xì)胞治療已用于脊髓損傷、運(yùn)動神經(jīng)元病、卒中后遺癥、癡呆、腦癱等疾病和損害患者的臨床神經(jīng)修復(fù)治療，能在一定程度上改善神經(jīng)功能和患者的生存質(zhì)量[18-74]；神經(jīng)調(diào)控（刺激）和腦機(jī)對話近年來發(fā)展迅速，對帕金森病、癲癇、昏迷等疾病患者是有價(jià)值的治療方法選擇[75-86]。生物工程和組織工程的修復(fù)技術(shù)在臨床探索中也顯示出治療前景[87-88]。與此同時(shí)，已制定出臨床技術(shù)或疾病的治療指南，前后已修定出臺四個版本的《中國神經(jīng)修復(fù)細(xì)胞治療臨床應(yīng)用指南》[89-92]；2016年制定出了《脊髓損傷神經(jīng)修復(fù)臨床治療指南》[93]。近年來美國、歐盟等啟動了腦計(jì)劃[94-95]，日本和中國正在跟進(jìn)制定出臺腦計(jì)劃項(xiàng)目，而這些腦計(jì)劃項(xiàng)目的研究目標(biāo)無一例外都將從三個方面推進(jìn)神經(jīng)修復(fù)學(xué)的發(fā)展：（1）增加對神經(jīng)機(jī)能包括感知運(yùn)動、植物神經(jīng)、精神心理、認(rèn)知、記憶、智力等損害或退變演變規(guī)律的認(rèn)識深度和廣度；（2）探索或發(fā)現(xiàn)神經(jīng)調(diào)控（刺激）和腦機(jī)對話、神經(jīng)重塑、神經(jīng)保護(hù)、軸突再生和側(cè)芽、結(jié)構(gòu)修補(bǔ)、神經(jīng)替代、神經(jīng)免疫調(diào)節(jié)、神經(jīng)再生及血管再生等修復(fù)機(jī)制的更深層次控制機(jī)制或新的神經(jīng)修復(fù)機(jī)制；（3）尋找更好神經(jīng)修復(fù)干預(yù)策略和治療方法。

同理，隨著細(xì)胞治療技術(shù)、組織工程技術(shù)、生物工程技術(shù)、納米材料技術(shù)、藥物研發(fā)和量子理論和技術(shù)等科技快速發(fā)展，醫(yī)學(xué)修復(fù)學(xué)也將在認(rèn)識疾病、探索修復(fù)機(jī)制和治療策略上更上一層樓。

六、展望

醫(yī)學(xué)修復(fù)學(xué)從開始發(fā)展就貫穿融合在臨床醫(yī)學(xué)、預(yù)防醫(yī)學(xué)、康復(fù)醫(yī)學(xué)中。

醫(yī)學(xué)修復(fù)學(xué)融合在臨床醫(yī)學(xué)中，主要是作為一種新的不同于傳統(tǒng)治療方法，從系統(tǒng)、器官、組織、細(xì)胞等不同層面上以修復(fù)的方式治療或改變疾病、損害或衰老的結(jié)構(gòu)和功能狀態(tài)。

修復(fù)學(xué)融合在預(yù)防醫(yī)學(xué)中，主要強(qiáng)化易受損結(jié)構(gòu)、功能的預(yù)防和延緩衰老進(jìn)程，維持人類生物體更長久的正常生理狀態(tài)。

修復(fù)學(xué)融合在康復(fù)醫(yī)學(xué)中，主要是從系統(tǒng)、器官、組織、細(xì)胞等不同層面上修復(fù)已被破壞的結(jié)構(gòu)和功能，恢復(fù)這些結(jié)構(gòu)和功能的完整性，與康復(fù)治療結(jié)合達(dá)到事半功倍治療效果。

神經(jīng)修復(fù)學(xué)[4-5,96-98]和口腔修復(fù)學(xué)（http://baike.baidu. com/subview/363988/9288115.htm）在醫(yī)學(xué)修復(fù)學(xué)系列學(xué)科發(fā)展中已走在前列，并形成完整的學(xué)科框架體系，包括學(xué)科概念、核心目的、學(xué)科理論、修復(fù)機(jī)制、治療策略、治療范圍、發(fā)展策略等；尤其是強(qiáng)調(diào)基礎(chǔ)與臨床轉(zhuǎn)化、治療和預(yù)防并重、修復(fù)與康復(fù)結(jié)合這三大戰(zhàn)略方針也一定是醫(yī)學(xué)修復(fù)學(xué)發(fā)展的戰(zhàn)略方針[14,97]。對于人體而言，修復(fù)無所不在，關(guān)鍵是我們要找到打開每一層次和環(huán)節(jié)的修復(fù)鑰匙；所有交叉學(xué)科如材料學(xué)、生物學(xué)、工程學(xué)、機(jī)械電子學(xué)等學(xué)科的技術(shù)進(jìn)步都有可能會改變或體現(xiàn)在醫(yī)學(xué)修復(fù)學(xué)中，這種修復(fù)探索的無限性必會使醫(yī)學(xué)修復(fù)學(xué)成為現(xiàn)代醫(yī)學(xué)的重要支撐學(xué)科和發(fā)展方向。

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Medical Restoratology—An important supporting discipline of modern medicine

Huang Hongyun1, Feng Shiqing2, Chen Lin3, Mao Gengsheng1, Zheng Zuncheng4.1Institute of Neurorestoratology, General Hospital of Armed Police Forces, Beijing 100039, China;2Department of Orthopedic, Tianjin Medical University General Hospital, T ianjin 300052, China;3Department of Neurosurgery, Tsinghua University Yuquan Hospital, Beijing 100040, China;4Department of Rehabilitation, Tai'an Central Hospital, Shandong 271000, China

Huang Hongyun, Email:hongyunh@gmail.com

With the rapid development of the medicine, it has shown four development directions and branches including clinical medicine, preventive medicine, rehabilitation medicine,and restorative medicine or medical restoratology. Medical restoratology has been paid more and more attention from the medical community, because it has as a medical disciplinary system been treating and preventing dysfunction of both human body structure and functions resulting from disease, damage as well as aging through restorative strategies. Especially cell therapy technology and bioengineering technology are accelerating the development of this disciplinary system. This review summarizes its development process, restorative mechanism, the basic concepts and coverage of the discipline, measures accelerating its development, and concept that "medical restoratology is an important direction of medical development, and one of the four carriages in modern medical discipline system".

Repair； Strategy； Mechanism； Tissue therapy； Biotechnology

2016-12-08）

（本文編輯：陳媛媛）

10.3877/cma.j.issn.2095-1221.2017.01.001

100039 北京，武警總醫(yī)院神經(jīng)修復(fù)學(xué)研究所1；300052天津醫(yī)科大學(xué)總醫(yī)院骨科2；100040 北京，清華大學(xué)玉泉醫(yī)院神經(jīng)外科3；271000 山東省泰安市中心醫(yī)院康復(fù)科4

黃紅云，Email：hongyunh@gmail.com

黃紅云，馮世慶，陳琳，等. 醫(yī)學(xué)修復(fù)學(xué)——現(xiàn)代醫(yī)學(xué)重要支撐學(xué)科[J/CD].中華細(xì)胞與干細(xì)胞雜志（電子版）, 2017, 7(1):1-6.