医学修复学——现代医学重要支撑学科

黄红云冯世庆陈琳毛更生郑遵成

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医学修复学
——现代医学重要支撑学科

黄红云1冯世庆2陈琳3毛更生1郑遵成4

随着医学快速发展，现已呈现为临床医学、预防医学、康复医学、修复医学或医学修复学四大发展方向和分支。医学修复学作为采用修复策略治疗和预防人类疾病和损害以及衰老导致的机体结构和功能障碍的医学学科体系正在受到医学界越来越多的关注，尤其是细胞治疗技术和生物工程技术正在催化这一学科体系加快发展。本文概述其发展概况、修复机制、学科基本概念和涵盖范围、加速推动其发展的举措，并提出“医学修复学是医学发展的重要方向，是现代医学学科体系的四驾马车之一”。

修复； 策略； 机制； 组织疗法； 生物技术

随着人类社会发展，医学现已成为自然科学和社会科学交汇的最重要学科之一。医学本身可分为临床医学、预防医学、康复医学、再生医学以及近十几年的修复医学或医学修复学等不同重点分支和发展方向；这些分支交叉融合发展，其核心目的是提高人类的健康水平或延年益寿。医学修复学相关研究、治疗和预防现在已受到越来越多的关注和重视，本文着重阐述和梳理医学修复学的发展概况和它发展的必然走向。

一、衰老的基本过程

生物体包括人类的衰老是一个必经的自然过程，疾病或外来损害会加速这一衰老或死亡过程。以细胞为例，任何一种细胞都有其自身的生命周期，当幼稚细胞或干、祖、前体细胞分化到功能细胞或成熟阶段时，其主要使命就是维持自身存活和发挥其生物功能，与此同时逐渐开始老化；在这个阶段如果受到外因意外损害或体内疾病造成内环境不利改变，细胞耐受性和顺应性就会降低，细胞自身的生命周期将缩短。组织、器官、系统和生物体也像细胞一样有其自身生命周期，除了自身衰老正常过程外，都有可能受到外因损害或内在疾病影响，而缩短其生命周期。

二、医学修复学发展概况

医学修复学或修复医学目前正处在发展早期，学科概念尚无统一认识和理念，现阶段主要有以下两种观点。

1.把修复医学视为临床医疗的一种治疗策略和方法[1]，它包括四个层次，（1）把蛋白或基因作为药物输入机体，如胰岛素、干扰素、生长激素和促红细胞生成素等；（2）细胞移植直接注射病变部位，或组织工程中把细胞作为种子置于材料形成组织或器官后移植；（3）干细胞移植；（4）纳米或更微小材料移植。

2.把修复医学视为基于修复器官功能和组织损伤的跨学科补充和替代医学（CAM）[2]，治疗方法包括营养补充剂、化学药物、植物药物和激素等替代治疗（https:// restorativemedicine.org/）。

在深入研究上述两种观点后，我们认为修复医学或医学修复学不仅仅是医疗方法，也不只是补充和替代医学，而是一种新的医学学科体系，这一医学学科的目的是“采用修复治疗和预防策略，通过修复机制，最大程度恢复和预防人类疾病和损害以及衰老导致的机体结构和功能障碍”。当临床医学对人体各系统采用常规治疗无能为力时，最终都需要通过修复机制和策略来改变和恢复受损的结构和功能。

以神经系统神经修复学发展过程为例，在人们过去的认知中，神经系统疾病、损害和自身衰老导致的结构和功能损害，尤其是损害后遗症期，被一直认为是无法改变的。先驱者最开始都是以探索改变神经结构和功能障碍的方法为主，得到神经结构和功能改善的现象，随后才进一步研究神经修复的机制[3-5]。

由于神经修复涉及多学科，从研究者自身学科角度就提出了一些本学科分支理念或作为一种治疗方法，如修复神经病学、修复神经外科学、修复神经科学、外科神经修复学、神经修复技术或疗法等[6-12]；但这些学科分支或技术的名称都无法涵盖和整合所有神经修复的内涵和外延，最后以神经修复学学科的建立才整合了全部与神经修复相交叉学科的相关研究内涵和外延[13-15]。

鉴于此，用医学修复学而不是修复医学命名这一体系应更为合适和准确，其系列分支可以分别命名为× ×修复学学科，如神经修复学、口腔修复学、肾脏修复学等。

三、医学修复学的修复机制

从修复机制上看，医学修复学机制主要有保护、信号调控、免疫调控、结构修复、替代、再生、促血管新生等，目前经修复治疗后只有很少部分的功能恢复是来自于再生机制。实际上再生就如同直角三角形是特殊三角形一样，它是一种特殊修复机制，仅仅是众多修复机制的其中之一，大多数功能恢复是来自于再生以外的其他修复机制；尤其在细胞治疗异军突起后，发现细胞旁分泌的保护和信号调控、免疫调控、结构修复、替代、促特殊组织和血管新生等各种修复机制作用就更加明显和突出，修复的机制包括再生但比再生更宽泛，用修复描述功能恢复的机制更准确。

因此从修复机制探索发展历程上看，再生医学只能是作为一个过渡阶段而成为医学修复学的一部分，而医学修复学涵盖的所有机制和治疗策略探索必将成为医学发展研究的重要方向。

四、医学修复学学科基本概念和涵盖范围

医学修复学是通过修复策略和机制来治疗和预防人类疾病和损害以及衰老导致的机体结构和功能障碍的医学学科体系。治疗和预防策略包括：细胞和组织移植、组织工程和生物工程技术、干预性修复手术、调控或刺激技术、药物（包括营养补充剂，化学药物、植物药物和激素等）、积极心理干预、补充和替代疗法以及其他有价值技术和手段。从医学学科系统基本构成来看，医学修复学涵盖范围或分支应包括神经修复学、心脏修复学、血管修复学、呼吸修复学、消化修复学（包括肝脏修复学、胰脏修复学和胃肠修复学）、肾脏修复学、骨修复学、内分泌修复学、免疫修复学和口腔修复学等学科。

机体作为生物体是一个完整系统，现代生物学将其向下分为系统、器官、组织、细胞、亚细胞器、分子和电子等不同层面。修复在不同层面采用不同方法和手段，并具有相应修复机制；以神经修复学治疗策略和机制为例[16]：（1）在器官层面上，采用神经嫁接、脊髓损伤内减压等方法，作用机制主要是神经结构修复、神经轴突再生、神经保护等；（2）在组织层面上采用细胞移植、组织工程方法，作用机制主要是神经重塑、突触重分布、神经网络重建、神经替代、神经再生和血管再生等；（3）在细胞层面上采用细胞移植、因子和药物治疗等方法，改变局部或整体环境，促使细胞结构和功能改变，作用机制主要是脱髓鞘修复、轴突再生、突触重分布、免疫调控和血管再生等；（4）在细胞器层面上采用药物等方法和促进自噬基因活性[17]，作用机制主要是神经保护、抗氧化、膜稳定与保护、清除损伤线粒体等；（5）在分子层面上采用基因转染或修饰、基因修复、重编程等生物工程技术、细胞治疗调节微环境改变分子结构和功能，其作用机制主要是神经调控、神经保护、免疫调控等；（6）在电子水平上采用细胞移植、电极植入等调控电信号，主要作用机制是神经调控、神经刺激或激活、脑机对话等；（7）未来可能在量子水平上会有相应方法和修复机制。

如同神经修复学的整体神经修复过程理论和神经修复法则一样[16]，在生理情况下生物体通过自身完整修复系统来对抗和抵御外来损害、疾病和自身衰老的致损因素，但当致损因素大到自身无法对抗和抵御时，就会处于结构和功能障碍等病理和病理生理的失衡状态，此时就需要采用人为的外来干预策略，才能维持或逆转被损害的结构和功能；这种通过自体或人为干预的不同修复机制维持和修复病理和病理生理状态结构和功能完整性的规律和定律可称为“整体医学修复过程理论和医学修复法则”。

五、加速推动医学修复学发展的举措

细胞治疗、生物工程和组织工程以及调控技术的研治进展，推动了医学修复学快速发展，尤其在细胞治疗技术和生物工程技术异军突起后，正在催化这一学科体系加快发展。以神经修复学为例，细胞治疗已用于脊髓损伤、运动神经元病、卒中后遗症、痴呆、脑瘫等疾病和损害患者的临床神经修复治疗，能在一定程度上改善神经功能和患者的生存质量[18-74]；神经调控（刺激）和脑机对话近年来发展迅速，对帕金森病、癫痫、昏迷等疾病患者是有价值的治疗方法选择[75-86]。生物工程和组织工程的修复技术在临床探索中也显示出治疗前景[87-88]。与此同时，已制定出临床技术或疾病的治疗指南，前后已修定出台四个版本的《中国神经修复细胞治疗临床应用指南》[89-92]；2016年制定出了《脊髓损伤神经修复临床治疗指南》[93]。近年来美国、欧盟等启动了脑计划[94-95]，日本和中国正在跟进制定出台脑计划项目，而这些脑计划项目的研究目标无一例外都将从三个方面推进神经修复学的发展：（1）增加对神经机能包括感知运动、植物神经、精神心理、认知、记忆、智力等损害或退变演变规律的认识深度和广度；（2）探索或发现神经调控（刺激）和脑机对话、神经重塑、神经保护、轴突再生和侧芽、结构修补、神经替代、神经免疫调节、神经再生及血管再生等修复机制的更深层次控制机制或新的神经修复机制；（3）寻找更好神经修复干预策略和治疗方法。

同理，随着细胞治疗技术、组织工程技术、生物工程技术、纳米材料技术、药物研发和量子理论和技术等科技快速发展，医学修复学也将在认识疾病、探索修复机制和治疗策略上更上一层楼。

六、展望

医学修复学从开始发展就贯穿融合在临床医学、预防医学、康复医学中。

医学修复学融合在临床医学中，主要是作为一种新的不同于传统治疗方法，从系统、器官、组织、细胞等不同层面上以修复的方式治疗或改变疾病、损害或衰老的结构和功能状态。

修复学融合在预防医学中，主要强化易受损结构、功能的预防和延缓衰老进程，维持人类生物体更长久的正常生理状态。

修复学融合在康复医学中，主要是从系统、器官、组织、细胞等不同层面上修复已被破坏的结构和功能，恢复这些结构和功能的完整性，与康复治疗结合达到事半功倍治疗效果。

神经修复学[4-5,96-98]和口腔修复学（http://baike.baidu. com/subview/363988/9288115.htm）在医学修复学系列学科发展中已走在前列，并形成完整的学科框架体系，包括学科概念、核心目的、学科理论、修复机制、治疗策略、治疗范围、发展策略等；尤其是强调基础与临床转化、治疗和预防并重、修复与康复结合这三大战略方针也一定是医学修复学发展的战略方针[14,97]。对于人体而言，修复无所不在，关键是我们要找到打开每一层次和环节的修复钥匙；所有交叉学科如材料学、生物学、工程学、机械电子学等学科的技术进步都有可能会改变或体现在医学修复学中，这种修复探索的无限性必会使医学修复学成为现代医学的重要支撑学科和发展方向。

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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）

（本文编辑：陈媛媛）

10.3877/cma.j.issn.2095-1221.2017.01.001

100039 北京，武警总医院神经修复学研究所1；300052天津医科大学总医院骨科2；100040 北京，清华大学玉泉医院神经外科3；271000 山东省泰安市中心医院康复科4

黄红云，Email：hongyunh@gmail.com

黄红云，冯世庆，陈琳，等. 医学修复学——现代医学重要支撑学科[J/CD].中华细胞与干细胞杂志（电子版）, 2017, 7(1):1-6.