尿激酶型纤溶酶原活化物和基质金属蛋白酶类在腹主动脉瘤组织中的表达

南方医科大学学报 ›› 2005, Vol. 25 ›› Issue (10): 1305-1307,1311.

尿激酶型纤溶酶原活化物和基质金属蛋白酶类在腹主动脉瘤组织中的表达

李艳¹, 张业伟²

1. 河南中医学院附属第一医院检验科, 河南, 郑州, 450000;
2. 南京医科大学附属第一医院肝脏移植中心, 江苏, 南京, 210029

出版日期:2005-10-20 发布日期:2005-10-20
基金资助:
收稿日期:2005-4-11。
作者简介:李艳,女,主管检验师

Expression of urokiase-type plasminogen activator and matrix metalloproteinases in human tissue of abdominal aortic aneurysm

LI Yan¹, ZHANG Ye-wei²

1. 河南中医学院附属第一医院检验科, 河南, 郑州, 450000;
2. 南京医科大学附属第一医院肝脏移植中心, 江苏, 南京, 210029

Online:2005-10-20 Published:2005-10-20

摘要/Abstract

摘要： 目的探讨尿激酶型纤溶酶原活化物(u-PA)和明胶酶A(MMP-2)、明胶酶B(MMP-9)在腹主动脉瘤(AAA)组织中的表达及产生的源泉。方法用u-PA和MMP-2、MMP-9单克隆抗体以免疫组织化学方法在30例AAA组织和30例正常腹主动脉组织切片上检测u-PA和MMP-2、MMMP-9抗原(蛋白);用u-PA的寡核苷酸探针和MMP-2、MMP-9的cDNA探针以原位杂交方法,在上述AAA组织和正常腹主动脉组织的冰冻切片上探测u-PA和MMP-2、MMP-9的mRNA。结果 u-PA和MMP-9主要在AAA组织中层和外膜巨噬细胞表达,在正常腹主动脉组织中无表达;MMP-2在AAA组织中主要由中层平滑肌细胞表达,在正常腹主动脉组织中无表达。结论由巨噬细胞产生的u-PA直接激活原MMP-2和原MMP-9,在AAA形成和扩张中起着关键性作用。

Abstract: Objective To explore the expression of urokinase-type plasminogen activator (u-PA) and matrix metalloproteinases in human abdominal aortic aneurysm (AAA) tissue. Methods Immunohistochemistry and in situ hybridization were employed to detect the protein and mRNA expression of u-PA, gelatinase A (MMP-2) and gelatinase B (MMP-9) in the tissue sections of 30 AAA specimens and 30 normal human abdominal aorta specimens. Results The expressions of u-PA and MMP-9 were mainly found in the macrophages in AAA tissue, but not in normal human abdominal aorta tissues. The expression of MMP-2 was found mainly in the smooth muscle cells in AAA tissues, but not in normal human abdominal aorta tissues. Conclusion u-PA produced by macrophages may immediately activate proMMP-2 and proMMP-9, which play a pivotal role in the formation and development of AAA.

中图分类号:

李艳¹, 张业伟². 尿激酶型纤溶酶原活化物和基质金属蛋白酶类在腹主动脉瘤组织中的表达[J]. 南方医科大学学报, 2005, 25(10): 1305-1307,1311.

LI Yan¹, ZHANG Ye-wei². Expression of urokiase-type plasminogen activator and matrix metalloproteinases in human tissue of abdominal aortic aneurysm[J]. Journal of Southern Medical University, 2005, 25(10): 1305-1307,1311.

参考文献

[1] Maggiano N, Larocca LM, Pinntelli M, et al. Detection of mRNA and hnRNA using a digoxigenin labeled cDNA probe by in situ hybridization on frozen tissue sections [J]. Histochem J, 1991, 23(19): 69-74.
[2] Carmeliet P, Moons L, Lijnen R, et al. Urokinase-generated plasmin activates matrixmetalloproteinases during aneurysm formation [J].Nat Genet, 1997, 17(11): 439-44.
[3] Shah PK. Inflammation, metalloproteinases, and increased proteolysis: an emerging pathophysiological paradigm in aortic aneurysm [J]. Circulation, 1997, 96(9): 2115-7.
[4] Thompson RW, Parks WC. Role of matrix meralloproteinases in abdominal aortic aneurysms [J]. Ann N Y Acad Sci, 1996, 800(11):157-74.
[5] Migntti P. Extracellular matrix remodeling by metallopro teinases abd okasminogen activators [J]. Kidney Int, 1995, 47(Suppl 49):12-4.
[6] Roldan AL, Cubellis MV, Masucci MT, et al. Cloning and expression of the receptor for humanurokonase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis [J].EMBO J, 1999, 16(21): 467-74.
[7] Vassali JD, Baccino D, Belin D, et al. A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinaes [J].J Cell Biol, 1985, 100(12): 86-92.
[8] Ellis V, Behrendt N, Dano K, et al. Plasminogen activation by receptor-bound urokinase, a kinetic study with both cell-associated and isolated receptor[J]. J Biol Chem, 1991, 266: 12752-8.
[9] Anidjar S, Salzmann JL, Gentric D, et al. Elastase induces experimentalaneurysms in rats [J]. Circulation, 2001, 82 (14):973-81.
[10] Matrisian LM. The matrix-degrading metalloproteinases [J]. Bioessays, 1992, 14(7): 455-62.
[11] Birkedal-Hansen H. Proteolytic remodeling ofextracellular matrix [J]. Cuur Opin Cell Biol, 1995, 7(7): 728-35.
[12] Okada Y, Agonoji Y, Naka K, et al. Matrix metalloproteinaes 9 (92 kDa gelatinase/type Ⅳ collagenase) from HT1080 human fibrosarcoma cells, purification and activation of the precursor and enxymic properties[J]. J Biol Chem, 1992, 267(14): 21712-9.
[13] Suxuki K, Eenhild J J, Morodomi T, et al. Mechanisms of activation of tissue procollagenase by metalloproteinase 3 (stomelysin) [J].Biochemistry, 1990, 29(9): 10261-70.
[14] Mazzieri R, Masiero L, Zanetta L, et al. Control of type Ⅳ collagenase activity by components of the urokinase-plasmin system regulatory mechanism with cell-bound reactants[J]. EMBO J, 2003,16(9): 2319-32.
[15] Mignatti P, Tsuboi R, Robbins E, et al. In vitro angiogenesis on the human amniotic membrane: requirement for basic fibroblast growth factor induced proteinases [J]. J Cell Biol, 2004, 108( 13): 671-82.
[16] Galis ZS, Muszynski M, Sukhova GK, et al. Cytokine-stimulated human vascular smooth muscle cells synthesize accomplishment of enzymes required for extracellular matrix digestion [J]. Circ Res,1994, 75(1): 181-89.
[17] Herron S, Unemori E, Wong M, et al. Connective tissue proteinases and inhibitor in abdominal aortic aneurysms, involvement of the vase vasorum in the pathogenesis of aortic anuysms [J]. Arterioscler Thromb Vasc Biol, 2001, 11(1): 1667-77.
[18] Szekanecz Z, Shah MR, Harlow LA, et al. Interleukin-8 and tumor necrosis factor-are involved in human aortic endothelial cell migration[J]. Pathobiology, 2004, 62(3): 134-9.
[19] White JV, Haas K, Phillips S, et al. Adventitial elastolysis is a primary event in aneurysm formation [J]. J Vasc Surg, 2003, 17(2):371-80.