机械牵伸调节TGF-β3/CREB抗肌腱粘连的实验研究

李帅峰; 邱洪九; 谢川江; 廖世亮; 熊雁

doi:10.16016/j.1000-5404.201904133

您当前的位置：

首页 >

文章列表页 >

机械牵伸调节TGF-β3/CREB抗肌腱粘连的实验研究

基础医学 | 更新时间：2026-01-09

- 机械牵伸调节TGF-β3/CREB抗肌腱粘连的实验研究
- Mechanical stretching enhances TGF-β3 and CREB expression to reduce tendon adhesion during tendon healing in rats
- 第三军医大学学报 2019年41卷第18期页码：1750-1757
- 作者机构：
  
  400042 重庆，陆军军医大学(第三军医大学)大坪医院骨科
- 作者简介：
  
  [ 熊雁，E-mail:xiongyandoctor@163.com XIONG Yan, E-mail: xiongyandoctor@163.com
- 基金信息：
  
  国家自然科学基金面上项目(81772330)
- DOI：10.16016/j.1000-5404.201904133
  中图分类号： R-332;R454.4;R686
- 收稿：2019-04-17，
  
  修回：2019-06-23，
  
  纸质出版：2019-09-30
- 稿件说明：
移动端阅览
李帅峰, 邱洪九, 谢川江, 等. 机械牵伸调节TGF-β3/CREB抗肌腱粘连的实验研究[J]. 第三军医大学学报, 2019,41(18):1750-1757.

Shuaifeng LI, Hongjiu QIU, Chuanjiang XIE, et al. Mechanical stretching enhances TGF-β3 and CREB expression to reduce tendon adhesion during tendon healing in rats[J]. Journal of Third Military Medical University, 2019, 41(18): 1750-1757.
李帅峰, 邱洪九, 谢川江, 等. 机械牵伸调节TGF-β3/CREB抗肌腱粘连的实验研究[J]. 第三军医大学学报, 2019,41(18):1750-1757. DOI： 10.16016/j.1000-5404.201904133.

Shuaifeng LI, Hongjiu QIU, Chuanjiang XIE, et al. Mechanical stretching enhances TGF-β3 and CREB expression to reduce tendon adhesion during tendon healing in rats[J]. Journal of Third Military Medical University, 2019, 41(18): 1750-1757. DOI： 10.16016/j.1000-5404.201904133.

摘要

目的

观察机械牵伸促大鼠肌腱愈合、抗肌腱粘连的作用，并探讨其对转化生长因子-β3(transforming growth factor-β3，TGF-β3)/环磷酸腺苷应答元件结合蛋白(cAMP response element binding protein

CREB)信号通路的影响。

方法

SD大鼠18只，双侧后趾建立屈趾肌腱损伤修复模型，按随机数字表法分为3组，每组6只。牵伸组术后予以持续1周的被动机械牵伸，损伤组术后不予以牵引，假手术组仅在手术中暴露肌腱，不损伤肌腱即关闭伤口。术后第1、2、4、8周通过解剖学观察、组织学检查、实时荧光定量PCR反应和免疫组化观察肌腱愈合情况和目的基因的表达水平。

结果

各时间点牵伸组肌腱较损伤组瘢痕粘连程度减轻，肉芽组织生成减少，细胞排列更加有序(

0.05)。愈合过程中牵伸组TGF-β3与CREB的mRNA水平在各时间点均显著高于损伤组，TGF-β1 mRNA的表达在术后早期(术后1周内)较损伤组明显降低(

0.05)，1周后2组差异无统计学意义。免疫组化染色结果提示牵伸组术后TGF-β3与CREB阳性表达强于损伤组，而TGF-β1阳性表达在术后1周时降低，差异具有统计学意义(

0.05)。

结论

机械牵伸可促进屈趾肌腱愈合并减少术后粘连，与TGF-β3和CREB表达的增加及TGF-β1表达的降低密切相关。

Abstract

Objective

To evaluate the effect of mechanical stretching in promoting tendon healing and reducing tendon adhesion during the healing of extensor flexor tendon in rats and its effects on the expression of transforming growth factor-β3 (TGF-β3) and cyclic AMP response element-binding protein (CREB).

Methods

Eighteen male SD rats were randomized into 3 equal groups and subjected to sham operation

flexor tendon injury of the second to fifth digits of the hind limbs without interventions (model group)

or flexor tendon injury with daily passive mechanical stretching of the tendon for 1 week after the operation. The tendon was exposed only without injuries in the sham-operated group. At 1

and 8 weeks after the operation

tendon healing of the rats was evaluated by anatomical observation and histological examination

and the expression of TGF-β1

TGF-β3 and CREB in the tendon was detected using real-time fluorescence quantitative PCR and immunohistochemistry.

Results

Compared with the model group

the rats in mechanical stretching group showed better tendon healing with reduced tendon adhesion

less granular tissue and more regular cell alignment in the tendon (

0.05). During tendon healing

the expression of TGF-β3 and CREB mRNAs in the injured tendon were significantly higher at all the time points and the expression of TGF-β1 mRNA at the first week after the operation was significantly lower in mechanical stretching group than in the model group (

0.05); TGF-β1 mRNA expression was comparable between the two groups at all the later time points. Immunohistochemical studies showed significantly stronger TGF-β3 and CREB expression in the injured tendons in the mechanical stretching group after the operation

and TGF-β1 expression began to decrease significantly at 1 week after the operation (

0.05).

Conclusion

Mechanical stretching can promote the healing of the flexor tendon and reduce postoperative tendon adhesion in close relation with increased expression of TGF-β3 and CREB and reduced expression of TGF-β1 in the early stage of tendon healing.

关键词

Keywords

references

KHANNA A, FRIEL M, GOUGOULIAS N, et al . Prevention of adhesions in surgery of the flexor tendons of the hand: what is the evidence?[J ] . Br Med Bull, 2009, 90: 85-109. DOI: 10.1093/bmb/ldp013.

LOISELLE A E, KELLY M, HAMMERT W C. Biological augmentation of flexor tendon repair: A challenging cellular landscape[J]. J Hand Surg Am, 2016, 41(1): 144-149;quiz 149. DOI: 10.1016/j.jhsa.2015.07.002.

KJAER M, LANGBERG H, HEINEMEIER K, et al . From mechanical loading to collagen synthesis, structural changes and function in human tendon[J ] . Scand J Med Sci Sports, 2009, 19(4): 500-510. DOI: 10.1111/j.1600-0838.2009.00986.x.

JIANG C Y, SHAO L, WANG Q J, et al . Repetitive mechanical stretching modulates transforming growth factor-β induced collagen synthesis and apoptosis in human patellar tendon fibroblasts[J ] . Biochem Cell Biol, 2012, 90(5): 667-674. DOI: 10.1139/o2012-024.

TESTA S, COSTANTINI M, FORNETTI E, et al . Combination of biochemical and mechanical cues for tendon tissue engineering[J ] . J Cell Mol Med, 2017, 21(11): 2711-2719. DOI: 10.1111/jcmm.13186.

汤锦波.手屈指肌腱损伤的临床修复效果[J].中华创伤骨科杂志, 2006, 8(1): 8-12. DOI: 10.3760/cma.j.issn.1671-7600.2006.01.003.

TANG J B. Current repairs of flexor tendon injuries in the hand[J]. Chin J Orthop Trauma, 2006, 8(1): 8-12. DOI: 10.3760/cma.j.issn.1671-7600.2006.01.003.

KILLIAN M L, CAVINATTO L, GALATZ L M, et al . The role of mechanobiology in tendon healing[J ] . J Shoulder Elbow Surg, 2012, 21(2): 228-237. DOI: 10.1016/j.jse.2011.11.002.

陈亮, 尹良军, 梁凯路, 等.大鼠跟腱损伤修复局部生长因子内源性表达变化的研究[J].重庆医学, 2012, 41(15): 1476-1478.DOI: 10.3969/j.issn.1671-8348.2012.15.008.

CHEN L, YIN L J, LIANG K L, et al . Study on change of endogenous expression of local growth factor in repair of rat achilles tendon injury[J ] . Chongqing Med, 2012, 41(15): 1476-1478. DOI: 10.3969/j.issn.1671-8348.2012.15.008.

KLIFTO C S, CAPO J T, SAPIENZA A, et al . Flexor tendon injuries[J ] . J Am Acad Orthop Surg, 2018, 26(2): e26-e35. DOI: 10.5435/jaaos-d-16-00316.

窦永峰, 房清敏, 王志刚, 等. TGF-β1抗体复合生物蛋白胶预防鞘管区屈肌腱粘连的组织学观察[J].中国矫形外科杂志, 2012, 20(16): 1489-1492. DOI: 10.3977/j.issn.1005-8478.2012.16.14.

DOU Y F, FANG Q M, WANG Z G, et al . The preventing effect of the compound of transforming growth factor-β1 antibody with fibrin glue (TGFβ1 Ab +FG) on postoperative adhesions in the chicken's flexor tendon in zone Ⅱ (no man's land)[J ] . Orthop J China, 2012, 20(16): 1489-1492. DOI: 10.3977/j.issn.1005-8478.2012.16.14.

MAJEWSKI M, HEISTERBACH P, JAQUIÉRY C, et al . Improved tendon healing using bFGF, BMP-12 and TGFβ1 in a rat model[J ] . Eur Cell Mater, 2018, 35: 318-334. DOI: 10.22203/eCM.v035a22.

姜士超, 刘珅, 范存义.肌腱粘连机制及预防的研究进展[J].中国修复重建外科杂志, 2013, 27(5): 633-636. DOI: 10.7507/1002-1892.20130139.

JIANG S C, LIU S, FAN C Y. Research progress of mechanism and prevention of peritendinous adhesions[J]. Chin J Repar Reconstr Surg, 2013, 27(5): 633-636. DOI: 10.7507/1002-1892.20130139.

熊雁, 张正治, 傅晓岚, 等.核心蛋白聚糖对兔肌腱细胞增殖及细胞周期的影响[J].第三军医大学学报, 2006, 28(17): 1761-1764. DOI: 10.3321/j.issn: 1000-5404.2006.17.009.

XIONG Y, ZHANG Z Z, FU X L, et al . Effect of decorin on proliferation and cell cycle of rabbit tendon cells in vitro [J ] . J Third Mil Med Univ, 2006, 28(17): 1761-1764. DOI: 10.3321/j.issn: 1000-5404.2006.17.009..

熊雁, 张正治, 可金星, 等.核心蛋白聚糖对兔屈趾肌腱损伤位点胶原纤维形成以及成纤维细胞增殖的延迟效应[J].中国临床康复, 2005, 9(30): 101-103. DOI: 10.3321/j.issn: 1673-8225.2005.30.032.

XIONG Y, ZHANG Z Z, KE J X, et al . Delayed effects of decorin on the formation of collagen fibers and the proliferation of fibroblasts at the injured site of the flexor tendon of toes in rabbits[J ] . Chin J Clin Rehabil, 2005, 9(30): 101- 103. DOI: 10.3321/j.issn: 1673-8225.2005.30.032.

XIA C S, YANG X Y, WANG Y Z, et al . Tendon healing in vivo and in vitro : neutralizing antibody to TGF-β improves range of motion after flexor tendon repair[J ] . Orthopedics, 2010, 33(11): 809. DOI: 10.3928/01477447-20100924-06..

FINNSON K W, MCLEAN S, DI GUGLIELMO G M, et al . Dynamics of transforming growth factor beta signaling in wound healing and scarring[J ] . Adv Wound Care, 2013, 2(5): 195-214. DOI: 10.1089/wound.2013.0429.

KUO C K, PETERSEN B C, TUAN R S. Spatiotemporal proteindistribution of TGF-betas, their receptors, and extracellular matrix molecules during embryonic tendon development[J]. Dev Dyn, 2008, 237(5): 1477-1489. DOI: 10.1002/dvdy.21547.

JIANG K, WANG Z M, DU Q Y, et al . A new TGF-β3 controlled-released chitosan scaffold for tissue engineering synovial sheath[J ] . J Biomed Mater Res A, 2014, 102(3): 801-807. DOI: 10.1002/jbm.a.34742.

MALLANO T, PALUMBO-ZERR K, ZERR P, et al . Activating transcription factor 3 regulates canonical TGFβ signalling in systemic sclerosis[J ] . Ann Rheum Dis, 2016, 75(3): 586-592. DOI: 10.1136/annrheumdis-2014-206214.

DENG L, LI Y, HUANG J M, et al . Effects of p-CREB-1 on transforming growth factor-β3 auto-regulation in hepatic stellate cells[J ] . J Cell Biochem, 2011, 112(4): 1046-1054. DOI: 10.1002/jcb.23017.

CHAN E C, DUSTING G J, GUO N, et al . Prostacyclin receptor suppresses cardiac fibrosis: role of CREB phosphorylation[J ] . J Mol Cell Cardiol, 2010, 49(2): 176-185. DOI: 10.1016/j.yjmcc.2010.04.006.

DENG X L, DENG L, WANG P, et al . Post-translational modification of CREB-1 decreases collagen Ⅰ expression by inhibiting the TGF-β1 signaling pathway in rat hepatic stellate cells[J ] . Mol Med Rep, 2016, 14(6): 5751-5759. DOI: 10.3892/mmr.2016.5926.

SCHILLER M, DENNLER S, ANDEREGG U, et al . Increased cAMP levels modulate transforming growth factor-beta/Smad-induced expression of extracellular matrix components and other key fibroblast effector functions[J ] . J Biol Chem, 2010, 285(1): 409-421. DOI: 10.1074/jbc.M109.038620.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

栀子苷改善CCl₄引起的小鼠肝纤维化损伤的实验研究

负载转化生长因子β3微球的壳聚糖三维支架的制备