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Experimental Study on Indomethacin Suppresses Matrix Metalloproteinasese Expression in Elastase-Induced AAA Model of Rat

Author: JiangShaoJie
Tutor: JingZaiPing
School: Second Military Medical University
Course: General Surgery
Keywords: Abdominal aortic aneurysm Matrix Metalloproteinase Inhibitor Immunohistochemistry in situ hybridization
CLC: R654.4
Type: Master's thesis
Year: 2001
Downloads: 45
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Abstract


Purpose: To investigate the effects of indomethacin, an inhibitor of macrophage MMP expression, attenuates aneurysmal degeneration in elastase-induced AAA model of rats. This study was to determine if treatment with indomethacin effectively suppresses MMPs expression within aneurysmal wall tissue of rat and to elucidate the mechanisms underlying this effect. Methods: Twenty-four adult male SD rats underwent 2-hour aortic perfusion with porcine pancreatic elastase(PPE). Eight animals received injections of saline and eight animals received 4mg/kg/day indomethacin for 7 days. Pre-perfusion, post-perfusion, and final aortic diameters(AD) were determined, and histology and in situ hybridization were performed. Results: Eight out of control group animals developed AAA, which no aneurysms were observed in the indomethacin-treated group (p< 0.05). Whereas AD increased 118±5% in control animals, the mean increase in the indomethacin-treated group was only 48%±4% (p < 0.05). Although animals in both groups demonstrated an inflammatory response dominated by macrophages, the marked destruction of medial elastin in the control group was not present in the treatment group, and the level of MMP-9 in animals treated with indomethacin was decreased. Conclusions: Matrix metalloproteinases(MMPs) are considered to play a central role in the pathogenesis of abdominal aortic aneurysms(AAAs), in which the development of aortic dilatation correlates with the infiltrate of inflammatory cells,and destruction of medial elastin. In addition to its recognized effects as a direct MMP antagonist, indomethacin has direct MMP-inhibiting properties in vitro, mightinfluence medial elastin degradation within rat aneurysm tissue byreducing monocyte/macrophage expression of at least one elastolyticmetal1proteinase, MMP-9. This study has demonstrated thatindomethacin inhibit aneurysm growth in the mode1, and trearmentwith it may be a particu1arly effective strategy fOr achieving MMPinhibition in patients with an tu.

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CLC: > Medicine, health > Surgery > Of surgery > Cardiovascular and lymphatic system surgery > Peripheral vascular
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