VEGF-C基因修飾的淋巴結移植促進淋巴內皮細胞再生的初步研究_《中國修復重建外科雜志》

作者：

陸南杭 , 張勇 , 馮自豪 , 亓發芝

復旦大學附屬中山醫院整形外科（上海，200032）;

關鍵詞：

淋巴結移植 VEGF-C 淋巴內皮細胞大鼠

DOI：

10.7507/1002-1892.20130136

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目的探討采用VEGF-C基因修飾的淋巴結移植對移植淋巴結周圍組織內淋巴內皮細胞再生的影響。方法取成年雄性SD大鼠36只，體重200.1～271.5 g，選取一側采用帶血管蒂淋巴結同側原位移植方法制備腋窩淋巴結移植模型后，隨機分為兩組（n=18），分別將1.5 × 108 PFU 帶Flag標簽的VEGF-C基因過表達腺病毒載體及空載腺病毒載體注射入實驗組及對照組大鼠移植淋巴結中。術后3 d，免疫熒光染色觀察淋巴結內帶Flag標簽蛋白的表達情況；術后1、2、4周，免疫熒光染色觀察移植淋巴結周圍組織內Prox-1蛋白的表達并計算其熒光密度值；術后2、4周，通過測定患肢皮下注射偶氮藍后大鼠血液在620 nm波長下吸光度（A）值，觀察淋巴回流功能改善情況，以正常大鼠（正常組）及淋巴結移植大鼠（空白對照組）作為對照。結果術后3 d實驗組及對照組移植淋巴結內均可檢測到帶Flag標簽蛋白的表達。術后1、2、4周，實驗組移植淋巴結周圍組織內Prox-1蛋白熒光密度值呈進行性增加，且均明顯強于對照組（P lt; 0.05）。正常組及空白對照組大鼠血液A值分別為0.539 ± 0.020及0.151 ± 0.007。術后2周實驗組及對照組A值分別為0.170 ± 0.011及0.168 ± 0.010，4周時分別為0.212 ± 0.016及0.197 ± 0.006，均顯著低于正常組（P lt; 0.05），但與空白組比較差異無統計學意義（P gt; 0.05）；實驗組及對照組間比較，差異亦無統計學意義（P gt; 0.05）。結論VEGF-C基因修飾的淋巴結移植能顯著促進移植淋巴結周圍組織內淋巴內皮細胞的再生，但在4周內不能改善大鼠患肢淋巴回流功能。

引用本文： 陸南杭,張勇,馮自豪,亓發芝. VEGF-C基因修飾的淋巴結移植促進淋巴內皮細胞再生的初步研究. 中國修復重建外科雜志, 2013, 27(5): 619-623. doi: 10.7507/1002-1892.20130136 復制

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1. Oremus M, Dayes I, Walker K, et al. Systematic review: conservative treatments for secondary lymphedema. BMC Cancer, 2012, 12: 6.
2. Lin CH, Ali R, Chen SC, et al. Vascularized groin lymph node transfer using the wrist as a recipient site for management of postmastectomy upper extremity lymphedema. Plast Reconstr Surg, 2009, 123(4): 1265-1275.
3. Becker C, Assouad J, Riquet M, et al. Postmastectomy lymphedema: long-term results following microsurgical lymph node transplantation. Ann Surg, 2006, 243(3): 313-315.
4. Saaristo AM, Niemi TS, Viitanen TP, et al. Microvascular breast reconstruction and lymph node transfer for postmastectomy lymphedema patents. Ann Surg, 2012, 255(3): 468-473.
5. Karkkainen MJ, Haiko P, Sainio K, et al. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol, 2004, 5(1): 74-80.
6. Küchler AM, Gjini E, Peterson-Maduro J, et al. Development of the zebrafish lymphatic system requires VEGF-C signaling. Curr Biol, 2006, 16(12): 1244-1248.
7. Yaniv K, Isogai S, Castranova D, et al. Live imaging of lymphatic development in the zebrafish. Nat Med, 2006, 12(6): 711-716.
8. Shin WS, Rockson SG. Animal models for the molecular and mechanistic study of lymphatic biology and disease. Ann N Y Acad Sci, 2008, 1131: 50-74.
9. Kanter MA, Slavin SA, Kaplan W. An experimental model for chronic lymphedema. Plast Reconstr Surg, 1990, 85(4): 573-580.
10. Shin WS, Szuba A, Rockson SG. Animal models for the study of lymphatic insufficiency. Lymphat Res Biol, 2003, 1(2): 159-169.
11. Tammela T, Saaristo A, Holopainen T, et al. Therapeutic differentiation and maturation of lymphatic vessels after lymph node dissection and transplantation. Nat Med, 2007, 13(12): 1458-1466.
12. Alitalo K, Tammela T, Petrocva TV. Lymphangiogenesis in development and human disease. Nature, 2005, 438(7070): 946-953.
13. Karkkainen MJ, Haiko P, Sainio K, et al. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol, 2004, 5(1): 74-80.
14. Foster DN, Min B, Foster LK, et al. Positive and negative cis-acting regulatory elements mediate expression of the mouse vascular smooth muscle alpha-actin gene. J Biol Chem, 1992, 267 (17): 11995-12003.
15. Mumprecht V, Roudnicky F, Detmar M. Inflammation-induced lymph node lymphangiogenesis is reversible. Am J Pathol, 2012, 180(3): 874-879.
16. Alam A, Herault JP, Barron P, et al. Heterodimerization with vascular endothelial growth factor receptor-2 (VEGFR-2) is necessary for VEGFR-3 activity. Biochem Biophys Res Commun, 2004, 324(2): 909-915.
17. Tammela T, Alitalo K. Lymphangiogenesis: Molecular mechanisms and future promise. Cell, 2010, 140(4): 460-476.
18. Song SH, Kim KL, Lee KA, et al. Tie1 regulates the Tie2 agonistic role of angiopoietin-2 in human lymphatic endothelial cells. Biochem Biophys Res Commun, 2012, 419(2): 281-286.
19. Nguyen VP, Chen SH, Trinh J, et al. Differential response of lymphatic, venous and arterial endothelial cells to angiopoietin-1 and angiopoietin-2. BMC Cell Biol, 2007, 8: 10.
20. Shioda H. Immunohistochemical demonstration of Angiopoietin-2 in lymphatic vascular development. Histochem Cell Biol, 2009, 131(2): 231-238.
21. Wu X, Liu NF. FOXC2 transcription factor: a novel regulator of lymphangiogenesis. Lymphology, 2011, 4(1): 35-41.
22. Hayashi H, Kume T. Foxc2 transcription factor as a regulator of angiogenesis via induction of integrin beta3 expression. Cell Adh Migr, 2009, 3(1): 24-26.
23. Sabine A, Agalarov Y, Maby-El Hajjami H, et al. Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation. Dev Cell, 2012, 22(2): 430-445.

《中國修復重建外科雜志》

VEGF-C基因修飾的淋巴結移植促進淋巴內皮細胞再生的初步研究

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《中國修復重建外科雜志》

VEGF-C基因修飾的淋巴結移植促進淋巴內皮細胞再生的初步研究

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