缓释碱性成纤维细胞生长因子预防胆管损伤修复术后 胆管瘫痕形成的实验研究*

南京大学学报(自然科学版) ›› 2012, Vol. 48 ›› Issue (6): 797–803.

缓释碱性成纤维细胞生长因子预防胆管损伤修复术后
胆管瘫痕形成的实验研究*

陶亮1，李强1** ，任吴祯1，戴建武2，丁义涛1**

出版日期:2015-07-31 发布日期:2015-07-31
作者简介: (1.南京大学医学院附属鼓楼医院肝胆外科，南京，210008:2.中国科学院遗传与发育生物学研究所，北京，100109)
基金资助:
南京市医学科技发展一般课题基金(YKK11087)

The prevention of bile duct scar formation after bile duct injury repair
by using sustained-release basic fibroblast growth factor

Tao Liang¹，Li Qiang¹，Ren Hao-Zhen¹，Dai Jian Wu²，Ding Yi-Tao¹

Online:2015-07-31 Published:2015-07-31
About author: (1. Department of Hepatobiliary Surgery,The Affiliated Drum Zower Hospital of Nanjing University Medical School
Nanjing,210008,China;2. State Key Laboratory of Molecular Developmental Biology,lnstitute of Genetics
and Developmental Biology,Chinese Academy of Sciences,Beijing, 100190,China)

摘要/Abstract

摘要： 探讨缓释碱性成纤维细胞生长因子(basic fibroblast growth factor, bFGF)对胆管损伤修复术后胆管癖痕形成的预防作用.通过分组实验，制备猪胆管部分缺损模型，运用加载缓释bFGF胶原膜及空白胶原膜修复缺损.比较术后1、2、3个月的肝功能变化并用病理切片和兔疫组化染色比较胆管愈合、
胶原增生及肌成纤维母细胞(myofibroblast, MFB)的表达情况.术后6个月胆道造影观察狭窄形成情况.结果显示:经缓释bFGF治疗后，胆管未出现癖痕性狭窄.与空白胶原膜组相比，胆汁淤积酶学指标中GGT和TBA显著降低，免疫组化提示MFY的表达显著降低，胶原排列及结构更接近于正常胆管.证明运用缓释bFGF胶原膜治疗胆管缺损可通过加速胆管愈合及下调MFB的表达有效的预防胆管损伤修复术后胆管瘫痕的形成.

Abstract: The over-healing is a major problem in the process of bile duct injury repair, It will cause malignant out comes because of stricture by scar formation, It is necessary to promote rapid-healing。[the injury to prevent scar formation, In our previous work，we produced a sustained-release basic fibroblast growth factor(bFUF). After adding to collagen membrane it could not only retain the activity of growth factor but also obtain the ability of sustained and site-targeting.ln our study,we used this material to repair a 2. 0 X 0. 5cm elliptical defect in the bile duct of pigs,and blank collagen membranes with same size were used as control. Before being sacrificed，the alanine aminotransferase (ALT)，y-glutamyltransferase(GGT),direct bilirubin(DBil)，and total bile acid(TBA) in both groups wrere detected and compared. After being sacrificed，the H & E staining and Masson’s trichrome staining of the neo-bile duct and the immunohistochemical staining of crSMA in both groups was observed and counted，the anti-crSMA antibody was used to mark the myofibroblast(MFB)which is an important factor in the process of scar formation.The cholangiog- raphy was performed under fluoroscopic guidance by cholecystostomy to evaluate if there was any evidence of strir
ture formation at 6 months. Hg-E staining showed the faster healing rate of nco-bile duct and less scar formation af- to treated by sustained-release bFUF, and the thickness of nco-bile duct was similar with normal bile duct at 3 weeks. Compared with control group,thc levels of GGT and TBA were significant low at all time points;immunohis- tochemical staining showed the expression of MFB was also significant low at all time points.The structure of colla- gen fibers was similar with the normal bile duct as showed by Masson’s trichrome staining, It is proved that using a sustained-release bFGF could effectively prevent postoperative bile duct scar formation by accelerating the healing rate of bile duct and dowrrregulating the expression of MFB.

陶亮1，李强1** ，任吴祯1，戴建武2，丁义涛1**
. 缓释碱性成纤维细胞生长因子预防胆管损伤修复术后
胆管瘫痕形成的实验研究*
[J]. 南京大学学报(自然科学版), 2012, 48(6): 797–803.

Tao Liang¹，Li Qiang¹，Ren Hao-Zhen¹，Dai Jian Wu²，Ding Yi-Tao¹. The prevention of bile duct scar formation after bile duct injury repair
by using sustained-release basic fibroblast growth factor
[J]. Journal of Nanjing University(Natural Sciences), 2012, 48(6): 797–803.

参考文献

[1]Nuzzo G,Giuliante F,Persiani R.The risk of bili ary ductal injury during laparoscopic cholecystec tomy. Journal De Chirurgie(Paris) ,2004，141(6): 343一353.
[2]Kapoor VK. Bile duct injury repair;when? what? who? J Hepatobiliary Pancreat Surg, 2007，14 (5):476一479.
[3]Geng Z M,Xu J，Liu Q G,et al. Study on mecha- nism of benign biliary stricture. Digestive Surger- y,2002,1(5):321一323.耿智敏，徐军，刘青
光等.良性胆管狭窄形成机制的研究.消化外科，2002，1(5):321一323.
[4]Andersson R,Eriksson K,Blind P J,et al, Iatrogenic bile duct injury一A cost analysis. HPB(Oxford)， 2008，10(6):416一419.
[5]Shimono K,Nose Y.The need to develop artificial bile ducts. Artificial Organs,1995, 19(2):115一116.
[6]Dou C Q,Zhou N X. Advances in research on tis- sue engineering artifical biledutt matrials. Medical Journal of Chinese People’s Liberation Army,
2007,32(3);276-277.(窦春青，周宁新.组织工程化人工胆管材料学研究进展.解放军医学杂志，2007，32 (3):276一299).
[7]Ornitz D M, Itoh N. Fibroblast growth factors. Genome Biology,2001 ,45(2):REVIEWS 3005.
[8]Nagase T，Hisatomi T，Koshima I , et al. Heterotopic ossification in the sacral pressure ulcer treated with basic fibroblast growth factor; Coincidence or side
effect? Journal of Plastic, Reconstructive &- Aes- thetic Surgery,2007,60(3):327.
[9]Zhao W X, Han Q Q,Lin H,et al, improved neo- vascularization and wound repair by targeting hu man basic fibroblast growth factor( bFGF) to fi
brin. Journal of Molecular Medicine, 2008,86 (10):1127一1138.
[10]Gomez N A，Zapatier J A，Vargas P E. Re;"Small intestinal submucosa as a bioscaffold for biliary tract regenerationl”.Surgery,2004，135(4):460.
[11]Miyazawa M,Toru T，Toshimitsu Y，et al. A tis-engineered artificial bile duct grown to resem- the native bile duct. American .Iournal of
Transplantation,2005,5(6):1541~1547.
[12]Xu Y，Geng Z M,Wang J B. Effect of basic fibro- blast growth factor on wound healing of bilioen- teric anastomose. Chinese Journal of Reparative
and Reconstrutive Surgery,2005，19(5):341一 343.(徐勇，耿智敏，土居邦.碱性成纤维细胞生长因子对肝肠吻合愈合的影响.
中国修复重建外科杂志，2005,19(5):341-343).
[13]Sun W J，Sun C K，Lin H,etal.The effect of col- lagen-binding NGF-β on the promotion of sciatic nerve regeneration in a rat sciatic nerve crush in-
jury model. Biomaterials，2009，30(27):4649 一4656.
[14]Chen W , Shi C，Yi S, et al. Bladder regeneration by collagen scaffolds with collagen binding human basicfi broblast growth factor. Journal of Urolo-
gy,2010，183(6);2432一2439.
[15]Shi C, Chen W, Zhao Y，et al. Regeneration of full-thickness abdominal wall defects in rats u- sing collagen scaffolds loaded with collagen-bind-
ing basic fibroblast growth factor. Biomatcrials, 2011，32(3):753一759.
[16]Li X,Sun H，Lin N,et al. Regeneration of uterine horns in rats by collagen scaffolds loaded with collagen-binding human basic fibroblast growth
factor. Biomaterials. 2011，32(32):8172一8181.
[17]Darby 1, Sakalli O, Gabbiani G.Alphxsmooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. Laboratory lnvestiga-
tion,1990,63(1):21一29.
[18]Xu J，Geng Z M, Ma Q Y. Microstructural and ul- trastructural changes in the healing process of bile duct trauma. Hepatobiliary Pancreatic Disea-
ses Internationa1,2003,2(2),295一299.

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