MMP-9与VEGF在成人肝血管瘤中的表达及其意义-东南大学学报医学版

MMP-9与VEGF在成人肝血管瘤中的表达及其意义

单位：1. 江苏省中医院消化肿瘤外科, 江苏南京 210029;
2. 江苏省省级机关医院呼吸科, 江苏南京 210024;
3. 南京医科大学第一附属医院肝脏移植中心, 江苏南京 210029

分类号：R575.29

出版年·卷·期（页码）：2014·33·第一期（66-70）

摘要：

目的：探讨MMP-9、VEGF、FLT1、KDR、FLT4在成人肝血管瘤中的表达及其临床意义。方法：收集成人肝血管瘤组织30例、正常肝组织15例，RT-PCR检测MMP-9、VEGF、FLT1、KDR、FLT4的mRNA表达，免疫组化法检测肝组织标本中MMP-9和VEGF的表达，蛋白质印迹法测定MMP-9蛋白的表达，明胶酶谱法检测标本中MMP-9和pro-MMP9的活性变化。结果：肝血管瘤中MMP-9 mRNA的表达量明显高于正常组织，VEGF、FLT1、KDR、FLT4的mRNA表达未见明显差异；免疫组化的检测结果与mRNA的趋势一致；肝血管瘤中MMP-9蛋白的表达及活性亦较正常组织明显增高。结论：MMP-9在成人肝血管瘤组织中高表达可能与基质降解重塑、内皮细胞迁移及管状结构形成有关。

Objective: To address the expression and clinical significance of matrix metalloproteinase-9(MMP-9),vascular endothelial growth factor(VEGF),FLT1,KDR and FLT4 in adults with hepatic hemangiomas. Methods: Thirty hepatic hemangioma patients and fifteen healthy subjects were included in this study. The mRNA levels of MMP-9, VEGF, FLT1, KDR and FLT4 were examined by polymerase chain reaction-based methods. Location and distribution of MMP-9 and VEGF protein expression were determined by immunohistochemistry. The activities of MMP-9 and pro-MM9 were examined by zymography and protein levels by Western blotting. Results: We observed a significant increase in tissue MMP-9 mRNA and protein levels in hepatic hemangioma compared to normal liver tissue. The activities of MMP-9 and pro-MM9 were also markedly elevated. However, no differences in mRNA and protein levels of VEGF were seen in hepatic hemangiomas of adults compared to normal subjects. Conclusion: Based on these findings, we propose that the elevation of MMP-9 is possible associated with extracellular matrix degradation, endothelial cell migration and tube formation.

参考文献：

[1] HERMAN P, COSTA M L, MACHADO M A, et al.Management of hepatic hemangiomas: a 14-year experience[J].J Gastrointest Surg, 2005, 9(6):853-859.
[2] GIULIANTE F, ARDITO F, VELLONE M, et al.Reappraisal of surgical indications and approach for liver hemangioma: single-center experience on 74 patients[J].Am J Surg, 2011, 201(6):741-748.
[3] KLEINMAN M E, GREIVES M R, CHURGIN S S, et al.Hypoxia-induced mediators of stem/progenitor cell trafficking are increased in children with hemangioma[J].Arterioscler Thromb Vasc Biol, 2007, 27(12):2664-2670.
[4] STORCH C, HOEGER P.Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action[J].Br J Dermatol, 2010, 163(2):269-274.
[5] PRZEWRATIL P, SITKIEWICZ A, WYKA K, et al.Serum levels of vascular endothelial growth factor and basic fibroblastic growth factor in children with hemangiomas and vascular malformations——preliminary report[J].Pediatr Dermatol, 2009, 26(4):399-404.
[6] 程桂丹, 陆枫林.肝癌中基质金属蛋白酶及其抑制因子的研究进展[J].东南大学学报:医学版, 2010, 29(2):215-220.
[7] MAHAJAN D, MILLER C, HIROSE K, et al.Incidental reduction in the size of liver hemangioma following use of VEGF inhibitor bevacizumab[J].J Hepatol, 2008, 49(5):867-870.
[8] ZHANG W J, YE L Y, WU L Q, et al.Morphologic, phenotypic and functional characteristics of endothelial cells derived from human hepatic cavernous hemangioma[J].J Vasc Res, 2006, 43(6):522-532.
[9] ITINTEANG T, BRASCH H D, TAN S T, et al.Expression of components of the renin-angiotensin system in proliferating infantile haemangioma may account for the propranolol-induced accelerated involution[J].J Plast Reconstr Aesthet Surg, 2011, 64(6):759-765.
[10] BREM H, GRESSER I, GROSFELD J, et al.The combination of antiangiogenic agents to inhibit primary tumor growth and metastasis[J].J Pediatr Surg, 1993, 28(10):1253-1257.
[11] LI A, DUBEY S, VARNEY M L, et al.IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis[J].J Immunol, 2003, 170(6):3369-3376.
[12] CAVALLO-MEDVED D, RUDY D, BLUM G, et al.Live-cell imaging demonstrates extracellular matrix degradation in association with active cathepsin B in caveolae of endothelial cells during tube formation[J].Exp Cell Res, 2009, 315(7):1234-1246.
[13] NEWBY A C.Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates[J].Cardiovasc Res, 2006, 69(3):614-624.
[14] HUANG P H, CHEN Y H, WANG C H, et al.Matrix metalloproteinase-9 is essential for ischemia-induced neovascularization by modulating bone marrow-derived endothelial progenitor cells[J].Arterioscler Thromb Vasc Biol, 2009, 29(8):1179-1184.

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