主動脈瘤是一種致死率很高的疾病，形成的過程中並無明顯症狀，因此在臨床上常是意外的被發現，被視為體內的不定時炸彈。截至目前，手術為治療主動脈瘤唯一的方式。臨床上的主動脈瘤病患，若無迫切的危險性並不會執行手術，致使收集的檢體皆為末期的動脈瘤，因此，我們對於動脈瘤的致病機轉，所知仍有限。動脈瘤在病理學上被定義為外徑膨大超過上下端血管50%。本研究採用蘭嶼豬來進行實驗，原因是豬的心血管系統與人類的相似度最高。實驗中，我們假設，改變腹主動脈內的血流狀態會誘導動脈瘤的形成。我們利用窄化的方式改變血液狀態來誘導主動脈瘤生成，並以組織染色來偵測過程中的變化。我們以臨床上廣泛使用的人工血管(Telfon-patch)，約2公分長，在腹主動脈距離分叉處約3公分處進行漏斗狀窄化，讓下端的管徑大約減半而上方則不變，導致窄化下端流速提高。在窄化手術後，我們將動物分成存活4週、8週、12週以及對照組，對照組亦以人工血管環繞但未進行窄化。Hematoxylin & eosin染色結果顯示血管在窄化後8週，於窄化的下游端處，內徑已膨大超過50%，窄化後12週變化更加顯著。而彈性纖維的染色結果顯示，在窄化後4週，彈性纖維的密度下降，在8週後，彈性纖維明顯減少，且有斷裂的現象，在12週後，其量更少。在窄化的上游端，彈性纖維亦有減少的現象，但變化不如下游端明顯，在腎動脈上游端的腹主動脈則無明顯差異。膠原蛋白的分布狀況，在窄化後12週，於窄化的下游端有減少的趨勢，而在上游端及腎動脈以上並無顯著的差異。我們亦以平滑肌細胞肌動蛋白(Smooth muscle α-actin)的免疫組織染色來偵測平滑肌細胞的變化，在窄化後12週，窄化下游端的平滑肌細胞明顯的減少。以上的結果與臨床上所觀察到動脈瘤的特徵相似，證實血管窄化可以誘導動脈瘤的生成。

Aneurysms have a high prevalence in aged populations and exhibit high mortality when rupture. Aneurysms are asymptomatic until the catastrophic event of rupture occurs. Up to date, surgery is the only valid treatment for aneurysm. Because most surgical samples come from late-stage aneurysm, the pathogenesis of aneurysm remains poorly understood. Macroscopically, aneurysm is defined as vascular dilatation that exceeds the outer diameter of normal segment by 50%. Microscopically, aneurysm is characterized by medial thinning with elastic fiber degradation and smooth muscle cell depletion. Abdominal aortic aneurysm (AAA), usually occurring between renal arteries and the iliac bifurcation, accounts for 80% of aneurysm. In this study, we attempted to establish an AAA model in porcinis because porcine cardiovascular system is recognized to be highly similar to that of human. Previous studies indicated that flow disturbance is closely associated with aneurysm formation. Therefore, we hypothesized that long-term coarctation of an infrarenal abdominal aorta segment leads to the formation of AAA. Isolated infrarenal aorta, approximately 3 cm away from the bifurcation of common iliac arteries, was coarctated with a 2-cm Teflon-patch so that vascular diameter decreased approximately 50% at the bottom of coarctated site without changing the top. The sham operational control received Teflon-patch wrapping but not coarctation. After the coarctation, downstream blood flow rate increased. Over 50% dilatation was detected in the distal aortic segments at 8 and 12 weeks after surgery. Concomitantly, medial thinning and adventitial hypertrophy were detected in hematoxylin-and-eosin stained cross sections. In addition, elastic fibers detected with Verhoeff’s staining exhibited lower density at four weeks post-coarctation and were even fewer and more fragmented at 8 and 12 weeks post-coarctation. Elastic fiber density also decreased but was less pronounced in the proximal segment whereas no significant changes were detected in the suprarenal aorta. Collagen fibers detected with Masson’s trichrome markedly increased in the adventitia at 8 weeks but decreased at 12 weeks post-coarctation. Smooth muscle cells detected with smooth muscle-specific α-actin decreased in the distal aortic segments at 12 weeks post-coarctation. These results indicate that changing flow pattern in terminal abdominal aorta with long-term coarctation induces abdominal aortic aneurysm.

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