肌腱粘连的机制及干预研究进展

doi:10.3969/j.issn.1674-8115.2022.08.017

摘要/Abstract

摘要：

肌腱粘连是肌腱损伤修复术后常见的并发症，其治疗棘手，是当前临床上亟待攻克的难题之一。近年来，随着医学科学的不断更新与发展，肌腱愈合机制研究不断深入，为术后肌腱粘连的防治与功能恢复提供了理论依据。防治肌腱粘连的关键在于抑制外源性愈合和炎症反应以及促进内源性愈合。肌腱粘连的发生主要与转化生长因子-β（transforming growth factor-β，TGF-β）、碱性成纤维细胞生长因子、血管内皮生长因子等细胞因子有关，另外TGF-β/Smad信号转导通路也较为重要。临床上改进缝合方法及早期康复活动对肌腱粘连的防治具有关键作用，其原理与力学载荷对细胞行为的影响相关；材料联合药物是当前防治肌腱粘连的研究热点，现有的防粘连膜主要发挥物理屏障作用，负载药物后通过抑制炎症反应、调控细胞增殖代谢、抗氧化应激、抑制TGF-β等途径可以实现高效抑制粘连。该文就近年来肌腱粘连的机制以及防治手段中手术、康复、材料、药物等方面的研究进展作一综述，以期促进基础研究的转化应用，为临床防治肌腱粘连提供参考。

关键词: 肌腱粘连, 创伤愈合, 肌腱损伤, 机制, 预防

Abstract:

As one of the clinical challenges, tendon adhesion is a common complication after the repair of tendon injuries and difficult to treat. In recent years, with the continuous updating and development of medical science, research into the mechanism of tendon healing has been advanced, which provides a theoretical basis for the prevention and treatment of tendon adhesion and functional recovery after surgery. The key to prevent tendon adhesion is to inhibit exogenous healing and inflammatory reaction and to promote endogenous healing. The occurrence of tendon adhesion is mainly related to transforming growth factor-β (TGF-β), basic fibroblast growth factor, vascular endothelial growth factor and other cytokines. Additionally, TGF-β/Smad signal transduction pathway is of significance. Clinically, improvement of suturing methods and early rehabilitation activities play an important role in the prevention and treatment of tendon adhesion, the principle of which is related to the effect of mechanical loading on cell behavior. The combination of materials and drugs is the current research hotspot in the prevention and treatment of tendon adhesion. The existing anti-adhesion membrane mainly acts as physical barrier, and the drug-loaded membrane can efficiently inhibit adhesion by inhibiting inflammatory responses, regulating cell proliferation and metabolism, reducing oxidative stress, and inhibiting TGF-β. This article presents a review of recent research progress in the mechanisms of tendon adhesion and interventions in the areas of surgery, rehabilitation, materials and drugs, in order to promote the transformation and application of basic research, which may provide reference significance for clinical prevention and treatment of tendon adhesion.

Key words: tendon adhesion, wound healing, tendon injury, mechanism, prevention

中图分类号:

R318

沙攀, 赵雪雯, 朱浩天, 高崇洲, 刘珅. 肌腱粘连的机制及干预研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(8): 1116-1121.

SHA Pan, ZHAO Xuewen, ZHU Haotian, GAO Chongzhou, LIU Shen. Research progress in the mechanism and intervention of tendon adhesion[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(8): 1116-1121.

参考文献 47

1	ROBINSON L S, BROWN T, O'BRIEN L. Cost, profile, and postoperative resource use for surgically managed acute hand and wrist injuries with emergency department presentation[J]. J Hand Ther, 2021, 34(1): 29-36.
2	LIU C J, BAI J B, YU K L, et al. Biological amnion prevents flexor tendon adhesion in zone Ⅱ: a controlled, multicentre clinical trial[J]. Biomed Res Int, 2019, 2019: 2354325.
3	ZHANG Q, YANG Y H, YILDIRIMER L, et al. Advanced technology-driven therapeutic interventions for prevention of tendon adhesion: design, intrinsic and extrinsic factor considerations[J]. Acta Biomater, 2021, 124: 15-32.
4	TITAN A L, FOSTER D S, CHANG J, et al. Flexor tendon: development, healing, adhesion formation, and contributing growth factors[J]. Plast Reconstr Surg, 2019, 144(4): 639e-647e.
5	YANG Q Q, ZHANG L Z, ZHOU Y L, et al. Morphological changes of macrophages and their potential contribution to tendon healing[J]. Colloids Surf B Biointerfaces, 2022, 209(Pt 1): 112145.
6	TSAI S L, NÖDL M T, GALLOWAY J L. Bringing tendon biology to heel: leveraging mechanisms of tendon development, healing, and regeneration to advance therapeutic strategies[J]. Dev Dyn, 2021, 250(3): 393-413.
7	LEONG N L, KATOR J L, CLEMENS T L, et al. Tendon and ligament healing and current approaches to tendon and ligament regeneration[J]. J Orthop Res, 2020, 38(1): 7-12.
8	HU Y P, HE J, HE L H, et al. Expression and function of Smad7 in autoimmune and inflammatory diseases[J]. J Mol Med (Berl), 2021, 99(9): 1209-1220.
9	ROBERTS J H, HALPER J. Growth factor roles in soft tissue physiology and pathophysiology[J]. Adv Exp Med Biol, 2021, 1348: 139-159.
10	SANG R L, LIU Y Y, KONG L Y, et al. Effect of acellular amnion with increased TGF-β and bFGF levels on the biological behavior of tenocytes[J]. Front Bioeng Biotechnol, 2020, 8: 446.
11	MAO W F, WU Y F, YANG Q Q, et al. Modulation of digital flexor tendon healing by vascular endothelial growth factor gene transfection in a chicken model[J]. Gene Ther, 2017, 24(4): 234-240.
12	NAM H Y, PINGGUAN-MURPHY B, ABBAS A A, et al. Uniaxial cyclic tensile stretching at 8% strain exclusively promotes tenogenic differentiation of human bone marrow-derived mesenchymal stromal cells[J]. Stem Cells Int, 2019, 2019: 1-16.
13	HAMMERMAN M, DIETRICH-ZAGONEL F, BLOMGRAN P, et al. Different mechanisms activated by mild versus strong loading in rat Achilles tendon healing[J]. PLoS One, 2018, 13(7): e0201211.
14	ZHANG J, XIAO C S, ZHANG X, et al. An oxidative stress-responsive electrospun polyester membrane capable of releasing anti-bacterial and anti-inflammatory agents for postoperative anti-adhesion[J]. J Control Release, 2021, 335: 359-368.
15	CHEN C T, CHEN C H, SHEU C, et al. Ibuprofen-loaded hyaluronic acid nanofibrous membranes for prevention of postoperative tendon adhesion through reduction of inflammation[J]. Int J Mol Sci, 2019, 20(20): 5038.
16	SHALUMON K T, SHEU C, CHEN C H, et al. Multi-functional electrospun antibacterial core-shell nanofibrous membranes for prolonged prevention of post-surgical tendon adhesion and inflammation[J]. Acta Biomater, 2018, 72: 121-136.
17	MENG J, YU P, TONG J, et al. Hydrogen treatment reduces tendon adhesion and inflammatory response[J]. J Cell Biochem, 2019, 120(2):1610-1619.
18	LEE Y W, FU S C, MOK T Y, et al. Local administration of Trolox, a vitamin E analog, reduced tendon adhesion in a chicken model of flexor digitorum profundus tendon injury[J]. J Orthop Translat, 2016, 10: 102-107.
19	LIANG Y, XU K T, ZHANG P, et al. Quercetin reduces tendon adhesion in rat through suppression of oxidative stress[J]. BMC Musculoskelet Disord, 2020, 21(1): 608.
20	蔡传栋, 路明宽, 王伟, 等. 肌腱粘连机制与预防的研究进展[J]. 国际骨科学杂志, 2020, 41(3): 129-133.
	CAI C D, LU M K, WANG W, et al. Research progress of mechanism and prevention of peritendinous adhesion[J]. Int J Orthop, 2020, 41(3): 129-133.
21	ZHOU Y L, ZHANG L Z, ZHAO W X, et al. Nanoparticle-mediated delivery of TGF-β1 miRNA plasmid for preventing flexor tendon adhesion formation[J]. Biomaterials, 2013, 34(33): 8269-8278.
22	CHANG J, THUNDER R, MOST D, et al. Studies in flexor tendon wound healing: neutralizing antibody to TGF-β1 increases postoperative range of motion[J]. Plast Reconstr Surg, 2000, 105(1): 148-155.
23	LEES V C, WARWICK D, GILLESPIE P, et al. A multicentre, randomized, double-blind trial of the safety and efficacy of mannose-6-phosphate in patients having Zone Ⅱ flexor tendon repairs[J]. J Hand Surg Eur Vol, 2015, 40(7): 682-694.
24	YASAK T, ÖZKAYA Ö, ERGAN ŞAHIN A, et al. The efficacy of angiotensin-converting enzyme inhibitors in preventing postoperative tendon adhesion formation: an experimental study in rats[J]. Acta Orthop Traumatol Turc, 2022, 56(1): 1-7.
25	ZHENG W, QIAN Y, CHEN S, et al. Rapamycin protects against peritendinous fibrosis through activation of autophagy[J]. Front Pharmacol, 2018, 9: 402.
26	周智, 左文山, 谢跃, 等. 5-氟尿嘧啶联合大清止血膜预防肌腱粘连的临床研究[J]. 疑难病杂志, 2014, 13(3): 291-293.
	ZHOU Z, ZUO W S, XIE Y, et al. Clinical research of joint 5-fluorouracil and Daqing hemostatic membrane in prevention of tendon adhesion[J]. Chin J Difficult Complicated Cases, 2014, 13(3): 291-293.
27	罗俊毅, 梁贵鸿, 李日洪, 等. 中药熏洗联合手法治疗手部屈肌腱修复术后粘连的疗效观察[J]. 中国实用医药, 2020, 15(25): 16-18.
	LUO J Y, LIANG G H, LI R H, et al. Observation on the curative effect of traditional Chinese medicine fumigation and washing combined with manipulation in the treatment of adhesion after hand flexor tendon repair[J]. Chin Pract Med, 2020, 15(25): 16-18.
28	王振堂, 宝莹娜, 李昶, 等. 复方当归注射液对肌腱粘连中成纤维细胞增殖抑制的研究[J]. 中华手外科杂志, 2019, 35(4): 293-296.
	WANG Z T, BAO Y N, LI C, et al. The study of inhibitory effect of compound angelica injection on fibroblast proliferation in tendon adhesion[J]. Chin J Hand Surg, 2019, 35(4): 293-296.
29	曾林如, 汤样华, 王楠. 天然水蛭素对肌腱成纤维细胞抑制作用的体外研究[J]. 中国医学创新, 2018, 15(5): 9-12.
	ZENG L R, TANG Y H, WANG N. Research on the inhibitory effect on tendon fibroblasts of natural hirudin in vitro[J]. Med Innov Chin, 2018, 15(5): 9-12.
30	YURDAKUL SıKAR E, SıKAR H E, TOP H, et al. Effects of Hyalobarrier gel and Seprafilm in preventing peritendinous adhesions following crush-type injury in a rat model[J]. Ulus Travma Acil Cerrahi Derg, 2019, 25(2): 93-98.
31	左强, 董乐乐, 樊建军. 透明质酸衍生物Seprafilm防粘连薄膜防止肌腱粘连的实验研究[J]. 中国修复重建外科杂志, 2011, 25(9): 1094-1098.
	ZUO Q, DONG L L, FAN J J. Experimental study on Seprafilm anti-adhesion membrane composed of hyaluronic acid derivative on prevention of tendon adhesion in rabbit[J]. Chin J Repar Reconstr Surg, 2011, 25(9): 1094-1098.
32	LIN L X, YUAN F, ZHANG H H, et al. Evaluation of surgical anti-adhesion products to reduce postsurgical intra-abdominal adhesion formation in a rat model[J]. PLoS One, 2017, 12(2): e0172088.
33	ZUKAWA M, OKABE M, OSADA R, et al. Effect of hyperdry amniotic membrane in preventing tendon adhesion in a rabbit model[J]. J Orthop Sci, 2022, 27(3): 707-712.
34	MANTI N, GUVERCIN Y, MERCANTEPE T, et al. Clinical and histologic evaluation of partial Achilles tendon injury repair with amniotic membrane in rats[J]. J Am Podiatr Med Assoc, 2022, 112(1): 20-055.
35	CHEN Q, LU H, YANG H. Chitosan prevents adhesion during rabbit flexor tendon repair via the sirtuin 1 signaling pathway[J]. Mol Med Rep, 2015, 12(3): 4598-4603.
36	ZOU J, LU M K, CHEN S, et al. Beeswax-inspired superhydrophobic electrospun membranes for peritendinous anti-adhesion[J]. Mater Sci Eng C Mater Biol Appl, 2020, 116: 111166.
37	ZEBIRI H, VAN DEN BERGHE H, SAYEGH S, et al. Synthesis of PLA-poly(ether urethane)-PLA copolymers and design of biodegradable anti-adhesive membranes for orthopaedic applications[J]. J Mater Chem B, 2021, 9(3): 832-845.
38	FAKHRAEI O, ALIMOHAMMADI M, MORADI A, et al. Nanofibrous polycaprolactone/chitosan membranes for preventing postsurgical tendon adhesion[J]. J Biomed Mater Res B Appl Biomater, 2022, 110(6): 1279-1291.
39	CHEN S H, CHOU P Y, CHEN Z Y, et al. Electrospun water-borne polyurethane nanofibrous membrane as a barrier for preventing postoperative peritendinous adhesion[J]. Int J Mol Sci, 2019, 20(7): E1625.
40	NADRI S, RAHMANI A, HOSSEINI S H, et al. Prevention of peritoneal adhesions formation by core-shell electrospun ibuprofen-loaded PEG/silk fibrous membrane[J]. Artif Cells Nanomed Biotechnol, 2022, 50(1): 40-48.
41	胡燕青, 蒋海, 李棋, 等. 不同肌腱缝合方法的生物力学比较研究[J]. 中国修复重建外科杂志, 2017, 31(10): 1208-1213.
	HU Y Q, JIANG H, LI Q, et al. Biomechanical study of different suture methods in repairing tendon rupture[J]. Chin J Repar Reconstr Surg, 2017, 31(10): 1208-1213.
42	POLYKANDRIOTIS E, BESROUR F, ARKUDAS A, et al. Flexor tendon repair with a polytetrafluoroethylene (PTFE) suture material[J]. Arch Orthop Trauma Surg, 2019, 139(3): 429-434.
43	安彪, 张哲敏, 段文旭, 等. 改良肌腱缝合技术预防屈肌腱粘连[J]. 中华手外科杂志, 2017, 33(6): 430-432.
	AN B, ZHANG Z M, DUAN W X, et al. Clinical application of modified tendon suture technique for prevention of flexor tendon adhesion[J]. Chin J Hand Surg, 2017, 33(6): 430-432.
44	ZHOU Y L, YANG Q Q, YAN Y Y, et al. Gene-loaded nanoparticle-coated sutures provide effective gene delivery to enhance tendon healing[J]. Mol Ther, 2019, 27(9): 1534-1546.
45	BILGEN F, DUMAN Y, BULUT Ö, et al. The effect of increasing the contact surface on tendon healing[J]. Arch Plast Surg, 2018, 45(4): 357-362.
46	GEORGESCU A V, MATEI I R, OLARIU O. Zone Ⅱ flexor tendon repair by modified brunelli pullout technique and very early active mobilization[J]. J Hand Surg Am, 2019, 44(9): 804.e1-804.e6.
47	杨占宇, 刘中华, 朱海波, 等. 屈肌腱修复术后肌腱粘连的康复治疗[J]. 实用手外科杂志, 2019, 33(2): 227-230.
	YANG Z Y, LIU Z H, ZHU H B, et al. Rehabilitation of tendon adhesion after flexor tendon repair[J]. J Pract Hand Surg, 2019, 33(2): 227-230.

[1]	张琳程, 钟华. 结节病的发病机制与临床治疗研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(7): 931-938.
[2]	王杨, 程佳月, 王振. 经颅直流电刺激作用机制的研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(7): 952-957.
[3]	张修齐, 沈柏用. 胰腺导管腺癌神经侵袭的细胞学机制研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(6): 833-838.
[4]	李燕, 江艳, 康琼芳, 陆群峰. 婴幼儿尿布性皮炎预防策略的最佳证据总结[J]. 上海交通大学学报（医学版）, 2022, 42(3): 357-363.
[5]	林艳艳, 许岩, 李慧. 儿童急性淋巴细胞白血病化学治疗常规药物耐药机制的研究进展[J]. 上海交通大学学报(医学版), 2022, 42(2): 211-217.
[6]	韩春红, 王洁, 洪洋, 童亚慧. 深静脉血栓形成机械预防知信行问卷的编制及信度和效度检验[J]. 上海交通大学学报(医学版), 2022, 42(1): 28-35.
[7]	蔡苗苗, 高艳虹. 肌少-骨质疏松症的研究进展[J]. 上海交通大学学报(医学版), 2021, 41(5): 678-683.
[8]	路明宽, 蔡传栋, 王伟, 范存义, 刘珅. 防肌腱粘连膜制备材料的研究进展[J]. 上海交通大学学报(医学版), 2021, 41(4): 550-553.
[9]	寇禧, 赵爱民. 羟氯喹应用于生殖免疫领域的研究进展[J]. 上海交通大学学报(医学版), 2021, 41(3): 380-385.
[10]	蔡传栋, 王非, 崔文国, 范存义, 刘珅. 基质金属蛋白酶响应性G4 PAMAM-IBU/GelMA水凝胶的构建及其特征研究[J]. 上海交通大学学报(医学版), 2021, 41(2): 140-146.
[11]	白娅娅，姚玮艳. 嗜酸性粒细胞性胃肠炎的诊断和治疗研究进展[J]. 上海交通大学学报(医学版), 2020, 40(8): 1152-1156.
[12]	路芳芳1，姚佳璐2，钮晓音3，翁震4#，何杨1, 4#. 阿苯达唑对小鼠动脉血管狭窄的干预效果及机制研究[J]. 上海交通大学学报(医学版), 2020, 40(5): 598-603.
[13]	叶惠玲，吕娜，范青. 抑郁症语义加工异常脑机制研究进展[J]. 上海交通大学学报(医学版), 2020, 40(5): 679-682.
[14]	倪优，陈晟. 抗 N-甲基-D-天冬氨酸受体脑炎发病机制及临床研究进展[J]. 上海交通大学学报（医学版）, 2019, 39(9): 1095-.
[15]	李莹莹 1，罗亚平 2，傅国辉 1, 2，陈诗慧 1. 胃泌素对白介素 1β诱导的大鼠软骨细胞分解代谢的抑制作用[J]. 上海交通大学学报（医学版）, 2019, 39(8): 861-.