Misra Sanjay, Fu Alex A, Anderson Jill L, Sethi Sanjeev, Glockner James F, McKusick Michael A, Bjarnason Haraldur, Woodrum David A, Mukhopadhyay Debabrata
Department of Radiology, Mayo Clinic College of Medicine, 200 First Street Southwest, Alfred 6460, Rochester, MN 55905, USA.
J Vasc Interv Radiol. 2008 Apr;19(4):587-94. doi: 10.1016/j.jvir.2008.01.005.
To determine whether a femoral arteriovenous (AV) fistula model in a rat was feasible and whether there is increased expression of matrix metalloproteinase (MMP)-2 and -9 and the tissue inhibitors of MMPs (TIMPs) at the venous stenosis of the fistula.
Fifteen male Sprague-Harley rats weighing 353 g +/- 26 underwent creation of an AV fistula between the left femoral artery and ipsilateral femoral vein, with the contralateral femoral vessels serving as controls. The animals were euthanized at day 14 (n = 5) and day 28 (n = 10) after fistula creation. Zymography and Western blot analysis for TIMP-1 and TIMP-2 were performed at the venous stenosis and in control vessels. Hematoxylin and eosin, Verhoeff-van Gieson, Masson trichrome, and alpha-smooth muscle staining were performed at the stenosis and in controls at day 28 in four animals. The intima/media ratio was determined at day 28.
By day 14, pro-MMP-2 measurements were 8.13 +/- 1.06 at the venous stenosis and 4.1 +/- 1.33 in controls (P < .05). By day 28, they had increased to 18.95 +/- 4.8 at the stenosis and 12.11 +/- 4.84 in controls (P < .05). By day 14, active MMP-2 measurements were 7.38 +/- 1.25 at the stenosis and 2.31 +/- 1.04 in controls (P < .05). By day 28, they had increased to 12.12 +/- 3.45 at the stenosis and 9.26 +/- 3.97 in controls (P < .05). By day 28, pro-MMP-9 measurements were 11.77 +/- 4.71 at the stenosis and 7.78 +/- 3.49 in controls (P < .05), with no difference at day 14. There was no difference in expression of TIMP-1 and TIMP-2. The average intima/media ratio of the stenosis increased by 28% versus controls, and the neointima was composed of primarily alpha-smooth muscle actin-positive cells.
A rat femoral AV fistula model was created with venous stenosis formation characterized by thickened neointima composed of alpha-smooth muscle actin-positive cells compared with controls. At the venous stenosis, there was increased expression of pro-MMP-2 and active MMP-2 by days 14 and 28, with significantly increased expression of pro-MMP-9 by day 28.
确定大鼠股动静脉（AV）瘘模型是否可行，以及在瘘管静脉狭窄处基质金属蛋白酶（MMP）-2和-9及其组织抑制剂（TIMP）的表达是否增加。
15只体重353 g±26 g的雄性Sprague-Harley大鼠，在左股动脉和同侧股静脉之间建立AV瘘，对侧股血管作为对照。在造瘘后第14天（n = 5）和第28天（n = 10）对动物实施安乐死。在静脉狭窄处和对照血管处进行TIMP-1和TIMP-2的酶谱分析和蛋白质印迹分析。在第28天，对4只动物的狭窄处和对照处进行苏木精-伊红染色、Verhoeff-van Gieson染色、Masson三色染色和α-平滑肌染色。在第28天测定内膜/中膜比值。
到第14天，静脉狭窄处前MMP-2的测量值为8.13±1.06，对照处为4.1±1.33（P < 0.05）。到第28天，狭窄处升至18.95±4.8，对照处为12.11±4.84（P < 0.05）。到第14天，狭窄处活性MMP-2的测量值为7.38±1.25，对照处为2.31±1.04（P < 0.05）。到第28天，狭窄处升至12.12±3.45，对照处为9.26±3.97（P < 0.05）。到第28天，狭窄处前MMP-9的测量值为11.77±4.71，对照处为7.78±3.49（P < 0.05），第14天无差异。TIMP-1和TIMP-2的表达无差异。狭窄处的平均内膜/中膜比值比对照增加了28%，新生内膜主要由α-平滑肌肌动蛋白阳性细胞组成。
建立了大鼠股AV瘘模型，其静脉狭窄形成的特征是与对照相比，新生内膜增厚，由α-平滑肌肌动蛋白阳性细胞组成。在静脉狭窄处，第14天和第28天时前MMP-2和活性MMP-2的表达增加，到第28天时前MMP-9的表达显著增加。
