緩釋bFGF膠原膜修復豬膽管缺損的實驗研究_《中國修復重建外科雜志》

作者：

陶亮 ¹ , 李強 ¹ , 任昊楨 ¹ , 戴建武 ² , 丁義濤 ¹

1南京大學醫學院附屬鼓樓醫院肝膽外科（南京，210008）;;
2 中國科學院遺傳與發育生物學研究所 △共同第一作者;

關鍵詞：

組織工程膽管缺損緩釋bFGＦ膠原微血管密度豬

DOI：

10.7507/1002-1892.20130046

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目的探討采用緩釋bFGF膠原膜修復豬膽管缺損的效果。方法中華實驗用豬28只，雌雄不限，體重15～30 kg；根據處理方法不同，將其隨機分為3組，其中實驗組12只，空白對照組12只，正常對照組4只。正常對照組不作處理；實驗組和空白對照組制備膽管壁缺損模型（長2 cm，寬1/3～2/3膽管周徑）后，分別采用2.0 cm × 1.0 cm × 0.5 mm緩釋bFGF膠原膜和空白膠原膜縫合修復。術后觀察實驗動物存活情況，并于術后1、2、3個月檢測肝功能變化，處死動物后行大體觀察；取膽管組織經HE及免疫組織化學染色，行微血管密度（microvessel density，MVD）及黏膜下腺體計數；術后3個月行經膽囊膽管膽道造影觀察。結果術后實驗動物均存活至實驗完成。術后1個月實驗組及空白對照組腹腔粘連均較嚴重，隨著時間延長，實驗組粘連較空白對照組明顯緩解。肝功能檢測示，除ALP在術后2、3個月實驗組及空白對照組均較正常對照組顯著下降（P lt; 0.05）外，其余各指標，如谷丙轉氨酶、總膽紅素和白蛋白術后各時間點組間比較，差異均無統計學意義（P gt; 0.05）。組織學及免疫組織化學染色觀察示，實驗組膽管腺體再生和上皮再生速度快于空白對照組，2個月即完成膽管上皮覆蓋，3個月與正常對照組相似，相應組織水腫和炎性浸潤均較空白對照組輕。術后1 個月實驗組黏膜下腺體計數及MVD值均顯著高于兩個對照組（P lt; 0.05），2個月后下降并穩定于正常對照組水平；空白對照組隨時間延長呈上升趨勢，術后1、2個月顯著低于實驗組和正常對照組（P lt; 0.05），3個月時達到并穩定于正常對照組水平。相關性分析表明，正常對照組、實驗組和空白對照組術后各時間點黏膜下腺體計數與MVD之間均成正相關（P lt; 0.01）。術后3個月造影顯示，實驗組、空白對照組均無膽管擴張及結石形成。結論緩釋bFGF膠原膜可通過促進新生血管再生等方式促進豬膽管缺損愈合。

引用本文： 陶亮,李強,任昊楨,戴建武,丁義濤. 緩釋bFGF膠原膜修復豬膽管缺損的實驗研究. 中國修復重建外科雜志, 2013, 27(2): 212-218. doi: 10.7507/1002-1892.20130046 復制

1.	Shimono K, Nosé Y. The need to develop artificial bile ducts. Artif Organs, 1995, 19(2): 115-116.
2.	陶亮, 李強, 丁義濤. 可降解膽管修復材料的研究進展. 中華肝膽外科雜志, 2011, 17 (9): 788-790.
3.	竇春青, 周寧新. 組織工程化人工膽管材料學研究進展. 解放軍醫學雜志, 2007, 32(3): 276-277.
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6.	徐勇, 耿智敏, 王居邠. 堿性成纖維細胞生長因子對膽腸吻合口愈合的影響. 中國修復重建外科雜志, 2005, 19(5): 341-343.
7.	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? J Plast Reconstr Aesthet Surg, 2007, 60(3): 327-329.
8.	李曉東, 孫文杰, 戴建武. 幾種常用生長因子的基因工程與創面修復. 中華損傷與修復雜志(電子版), 2007, 2(1): 51-54.
9.	Zhao WX, Han Q, Lin H, et al. Improved neovascularization and wound repair by targeting human basic fibroblast growth factor (bFGF) to fibrin. J Mol Med (Berl), 2008, 86(10): 1127-1138.
10.	Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat, 1995, 36(2): 169-180.
11.	Miyazawa M, Torii T, Toshimitsu Y, et al. A tissue engineered artificial bile duct grown to resemble the native bile duct. Am J Transplant, 2005, 5(6): 1541-1547.
12.	Aikawa M, Miyazawa M, Okamoto K, et al. A novel treatment for bile duct injury with a tissue-engineered bioabsorbable polymer patch. Surgery, 2010, 147(4): 575-580.
13.	Rosen M, Ponsky J, Petras R, et al. Small intestinal submucosa as a bioscaffold for biliary tract regeneration. Surgery, 2002, 132(3): 480-486.
14.	Gómez NA, Zapatier JA, Vargas PE. Re: “Small intestinal submucosa as a bioscaffold for biliary tract regeneration”. Surgery, 2004, 135(4): 460.
15.	Ismail A, Ramsis R, Sherif A, et al. Use of human amniotic stem cells for common bile duct reconstruction: vascularized support of a free amnion graft. Med Sci Monit, 2009, 15(9): BR243-247.
16.	Nakashima S, Nakamura T, Miyagawa K, et al. In situ tissue engineering of the bile duct using polypropylene mesh-collagen tubes. Int J Artif Organs, 2007, 30(1): 75-85.
17.	Nakashima S, Nakamura T, Han L, et al. Experimental biliary reconstruction with an artificial bile duct using in situ tissue engineering technique. Inflammation and Regeneration, 2007, 27(6): 579-585.
18.	Sun W, Sun C, Lin H, et al. The effect of collagen-binding NGF-beta on the promotion of sciatic nerve regeneration in a rat sciatic nerve crush injury model. Biomaterials, 2009, 30(27): 4649-4656.
19.	Chen W, Shi C, Yi S, et al. Bladder regeneration by collagen scaffolds with collagen binding human basicfi broblast growth factor. J Urol, 2010, 183(6): 2432-2439.
20.	Shi C, Chen W, Zhao Y, et al. Regeneration of full-thickness abdominal wall defects in rats using collagen scaffolds loaded with collagen-binding basic fibroblast growth factor. Biomaterials, 2011, 32(3): 753-759.
21.	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): 8172-8181.

1. Shimono K, Nosé Y. The need to develop artificial bile ducts. Artif Organs, 1995, 19(2): 115-116.
2. 陶亮, 李強, 丁義濤. 可降解膽管修復材料的研究進展. 中華肝膽外科雜志, 2011, 17 (9): 788-790.
3. 竇春青, 周寧新. 組織工程化人工膽管材料學研究進展. 解放軍醫學雜志, 2007, 32(3): 276-277.
4. Ornitz DM, Iton N. Fibroblast growth factors. Grnome Biol, 2001, 2(2): REVIEWS3005.
5. Nakamura S, Nambu M, Ishizuka T, et al. Effect of controlled release of fibroblast growth factor-2 from chitosan/fucoidan micro complex-hydrogel on in vitro and in vivo vascularization. J Biomed Mater Res A, 2008, 85(3): 619-627.
6. 徐勇, 耿智敏, 王居邠. 堿性成纖維細胞生長因子對膽腸吻合口愈合的影響. 中國修復重建外科雜志, 2005, 19(5): 341-343.
7. 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? J Plast Reconstr Aesthet Surg, 2007, 60(3): 327-329.
8. 李曉東, 孫文杰, 戴建武. 幾種常用生長因子的基因工程與創面修復. 中華損傷與修復雜志(電子版), 2007, 2(1): 51-54.
9. Zhao WX, Han Q, Lin H, et al. Improved neovascularization and wound repair by targeting human basic fibroblast growth factor (bFGF) to fibrin. J Mol Med (Berl), 2008, 86(10): 1127-1138.
10. Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat, 1995, 36(2): 169-180.
11. Miyazawa M, Torii T, Toshimitsu Y, et al. A tissue engineered artificial bile duct grown to resemble the native bile duct. Am J Transplant, 2005, 5(6): 1541-1547.
12. Aikawa M, Miyazawa M, Okamoto K, et al. A novel treatment for bile duct injury with a tissue-engineered bioabsorbable polymer patch. Surgery, 2010, 147(4): 575-580.
13. Rosen M, Ponsky J, Petras R, et al. Small intestinal submucosa as a bioscaffold for biliary tract regeneration. Surgery, 2002, 132(3): 480-486.
14. Gómez NA, Zapatier JA, Vargas PE. Re: “Small intestinal submucosa as a bioscaffold for biliary tract regeneration”. Surgery, 2004, 135(4): 460.
15. Ismail A, Ramsis R, Sherif A, et al. Use of human amniotic stem cells for common bile duct reconstruction: vascularized support of a free amnion graft. Med Sci Monit, 2009, 15(9): BR243-247.
16. Nakashima S, Nakamura T, Miyagawa K, et al. In situ tissue engineering of the bile duct using polypropylene mesh-collagen tubes. Int J Artif Organs, 2007, 30(1): 75-85.
17. Nakashima S, Nakamura T, Han L, et al. Experimental biliary reconstruction with an artificial bile duct using in situ tissue engineering technique. Inflammation and Regeneration, 2007, 27(6): 579-585.
18. Sun W, Sun C, Lin H, et al. The effect of collagen-binding NGF-beta on the promotion of sciatic nerve regeneration in a rat sciatic nerve crush injury model. Biomaterials, 2009, 30(27): 4649-4656.
19. Chen W, Shi C, Yi S, et al. Bladder regeneration by collagen scaffolds with collagen binding human basicfi broblast growth factor. J Urol, 2010, 183(6): 2432-2439.
20. Shi C, Chen W, Zhao Y, et al. Regeneration of full-thickness abdominal wall defects in rats using collagen scaffolds loaded with collagen-binding basic fibroblast growth factor. Biomaterials, 2011, 32(3): 753-759.
21. 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): 8172-8181.

《中國修復重建外科雜志》

緩釋bFGF膠原膜修復豬膽管缺損的實驗研究

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《中國修復重建外科雜志》

緩釋bFGF膠原膜修復豬膽管缺損的實驗研究

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