| Background Abdominal aortic aneurysm(AAA) is a serous disease which endangers the life of the people. In spite of the fact that much advance has been made in surgical treatment, the operative mortality rate of open surgery is still as high as 3-5%. The optimal management of small AAA (D<5cm) is controversial, some recommend early surgery, and others advocate ultra-sound scan surveillance unless a large threshold size is reached or rapid expansion occurs. As a novel approach to the disease endovascular grafting exclusion (EVGE) has brought hope to improve the security of surgical treatment. But the long term result of the technique is uncertain for aneurysm neck dilation and leakage after operation. With the progress of the study on pathogenesis of AAA, we get to know that aneurismal dilation is accompanied by marked loss of elastin from the tunica medium, and the elastase ,collagenase and gelatinase activity is increased within the aneurismal aortic wall. It brings much hope to solve the problem of small aneurysm and EVGE. To investigate the role of elastin and collagen degeneration by matrix metalloprotein (MMP) in the early stage of aneurysm dilation, a improved elastase-induced rat AAA model is constructed. And MMP-2,MMP-9 is detected by immunohistochemistry and in situ hybridization ways continuously in elastase induced AAA. After elastase perfusion, the rats are given doxycycline to observe the change of MMP-2,MMP-9expression. Methods: 192 Wistar rats underwent a 120 min perfusion of the abdominal aorta with or without 50 U/ml porcine pancreatic elastase and were then treated with either subcutaneous doxycycline (25mg/d;n=24) or saline solution ve (n=24) or nothing (n=144). Aortic diameter was measured before and after elastase perfusion was performed and before the rats were killed at 0,2,7 or 14 days, and AAAs were defined as an increase in aortic diameter to at least twice that before perfusion. At death the aortic tissues were either perfusion-fixed for histologic evaluation or extracted for Ihc and ish evaluation.Results: 1. The aortic diameter progress to aneurysm dimension among 30min,60min,120min perfusion of elastase and has no difference. Histology study revealed loss of elastin in the media of the aorta.2. immunohistochemistry and in situ hybridization study revealed MMP-2 increased (2-14 d) consistently, MMP-9 reached to peak on 7th day after elastase perfusion, 3. Aortic diameter was not different between groups at 0 or 2 days, but it was significantly less in animals treated with doxycycline at both 7 and 14 days ( p<0.01). By histologic assessment doxycycline prevented the structural deterioration of aortic elastin without decreasing the influx of inflammatory cells. Increased aortic wall production of MMP-9 observed in a saline solution-treated control group was markedly suppressed in animals treated with doxycycline at 7th day.Conclusion: 1. It is possible to shorten the elastase perfusion time from 120-30min in the elastasa -induced rat aneurysm model. The shortening of infusiontime reduces experimental time effectively.2. MMP-2 play a main role in extracellular matrix degradation of abdominal aortic aneutysms tunica media. 3.Treatment with an MMP-inhibiting doxycycline inhibits the development of experimental AAA in vivo. This inhibition may be due to selective blockade of elastolytic MMP expression. Additional experiments, however, are necessitated to fully delineate this process. |
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