Holmes D R, Wester W, Thompson R W, Reilly J M
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Vasc Surg. 1997 May;25(5):810-5. doi: 10.1016/s0741-5214(97)70210-6.
The purpose of this study was to evaluate the expression of prostaglandin E2 (PGE2) and the two cyclooxygenase isoforms (cox1 and cox2) in human abdominal aortic aneurysm (AAA) tissue.
Ten specimens each of normal aortas and aneurysmal aortas were collected and used for histologic analysis and whole organ culture. An enzyme-linked immunosorbent assay for PGE2 was performed on the media from the aortic explant whole organ culture. An immunohistochemical analysis for PGE2 was performed, as was in situ hybridization for cox1 and cox2 on tissue sections.
PGE2 production of AAA specimens was found to be 67,287 +/- 27,303 pg/ml as compared with 1698 +/- 858 pg/ml for normal aortic specimens (p < 0.001). PGE2 was localized by immunohistochemical analysis to the inflammatory infiltrate in AAAs. Minimal expression was noted in normal aortas. Using in situ hybridization, little expression of cox1 was noted in either the normal or the AAA specimens. Cox2 was expressed by macrophage-like cells within the inflammatory infiltrate of the AAA specimens but was not significantly expressed in the normal aorta.
The expression of PGE2 is associated with the pathogenesis of human AAAs. Its expression is localized to macrophage-like cells within the inflammatory infiltrate and is controlled by the cox2 isoform of cyclooxygenase. Cox2 is, therefore, a potential target for pharmacotherapy of AAAs.
本研究旨在评估前列腺素E2(PGE2)及两种环氧化酶同工型(cox1和cox2)在人腹主动脉瘤(AAA)组织中的表达情况。
收集10份正常主动脉和动脉瘤主动脉标本,用于组织学分析和全器官培养。对主动脉外植体全器官培养的培养基进行PGE2的酶联免疫吸附测定。对组织切片进行PGE2的免疫组织化学分析以及cox1和cox2的原位杂交。
发现AAA标本的PGE2产量为67,287±27,303 pg/ml,而正常主动脉标本为1698±858 pg/ml(p<0.001)。通过免疫组织化学分析,PGE2定位于AAA中的炎性浸润部位。在正常主动脉中观察到极少的表达。使用原位杂交,在正常或AAA标本中均未观察到cox1的明显表达。Cox2在AAA标本炎性浸润内的巨噬细胞样细胞中表达,但在正常主动脉中未显著表达。
PGE2的表达与人AAA的发病机制相关。其表达定位于炎性浸润内的巨噬细胞样细胞,并受环氧化酶的cox2同工型控制。因此,Cox2是AAA药物治疗的潜在靶点。