Eskandari Mark K, Vijungco Joseph D, Flores Amy, Borensztajn Jayme, Shively Vera, Pearce William H
Division of Vascular Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
J Surg Res. 2005 Feb;123(2):289-93. doi: 10.1016/j.jss.2004.07.247.
Matrix metalloproteinases (MMPs) are known elastolytic mediators of abdominal aortic aneurysm (AAA) degeneration, and their activity is tightly regulated by the presence of tissue inhibitors of MMPs (TIMPs). Imbalances in this system may be instrumental in compromising arterial wall integrity. The aim of this study was to show that, in an elastase-induced murine model of aneurysm formation, TIMP-1 has a protective effect.
Twenty-four wild-type (TIMP-1+/+) and 22 knockout (TIMP-1-/-) mice underwent laparotomy and isolation of the infrarenal aorta. A polyethylene catheter was inserted into the aorta and dilute pancreatic elastase (0.39 Units/ml) was infused over 5 min using a perfusion pump. Pre- and postinfusion maximal aortic diameters were obtained in triplicate for each animal using NIH Image. Final aortic measurements were obtained 14 days later, prior to perfusion fixation with 10% buffered Formalin. Aortic specimens were sectioned and stained. Statistical analysis was performed using the Student's t test.
TIMP-1-/- mice demonstrated a significant postinfusion diameter increase compared to wild-types after elastase, which was not seen after saline infusion. At sacrifice, TIMP-1-/- mice, following both saline and elastase infusion, showed a significant increase in maximal aortic diameter relative to postinfusion measurements compared to TIMP-1+/+ mice.
TIMP-1-/- mice develop larger aneurysms than TIMP-1+/+ mice. This study illustrates the protective effects of TIMP-1 in an experimental AAA model and may provide a means for pharmacologically controlling aneurysm growth.
基质金属蛋白酶（MMPs）是已知的腹主动脉瘤（AAA）退变的弹性蛋白酶解介质，其活性受基质金属蛋白酶组织抑制剂（TIMPs）的存在严格调控。该系统失衡可能有助于损害动脉壁完整性。本研究的目的是表明，在弹性蛋白酶诱导的小鼠动脉瘤形成模型中，TIMP-1具有保护作用。
24只野生型（TIMP-1+/+）和22只基因敲除型（TIMP-1-/-）小鼠接受剖腹术并分离肾下腹主动脉。将一根聚乙烯导管插入主动脉，使用灌注泵在5分钟内注入稀释的胰弹性蛋白酶（0.39单位/毫升）。使用NIH Image对每只动物在输注前后重复测量三次最大主动脉直径。14天后，在用10%缓冲福尔马林进行灌注固定之前，获得最终主动脉测量值。将主动脉标本切片并染色。使用学生t检验进行统计分析。
与野生型小鼠相比，TIMP-1-/-小鼠在弹性蛋白酶输注后显示出输注后直径显著增加，而在输注生理盐水后未观察到这种情况。处死时，与TIMP-1+/+小鼠相比，TIMP-1-/-小鼠在输注生理盐水和弹性蛋白酶后，相对于输注后测量值，最大主动脉直径显著增加。
TIMP-1-/-小鼠比TIMP-1+/+小鼠形成更大的动脉瘤。本研究说明了TIMP-1在实验性AAA模型中的保护作用，并可能为药物控制动脉瘤生长提供一种方法。
