乙酰肝素酶在腹主动脉瘤发病中的作用

Involvement of heparanase in human abdominal aortic aneurysm

目的 了解乙酰肝素酶在腹主动脉瘤 (AAA)发病中的作用 ,探讨AAA新的发病机制。方法 选取 2 0例人体肾下AAA、5例正常腹主动脉 (NA)及 5例原发性肝细胞癌 (HCC)组织标本 ,采用Northern杂交、免疫组织化学及计算机图像分析技术 ,检测乙酰肝素酶及其底物硫酸乙酰肝素酶蛋白多糖 (HSPG)的表达以及微血管增生水平。结果 AAA组织乙酰肝素酶水平明显高于NA(P <0 .0 1) ,而相当于HCC(P >0 .0 5 ) ;HSPG表达则与之相反 ,与乙酰肝素酶水平及微血管密度均呈显著负相关。乙酰肝素酶与HSPG在腹主动脉 (瘤 )均以内外膜分布为主。结论 乙酰肝素酶在基质水平参与腹主动脉结构损伤与重构 ,促进AAA形成。

Objective To determine whether heparanase might participate the formation of abdominal aortic aneurysms (AAA) and explore a novel pathogenesis for it. Methods Total RNA was extracted from 20 tissue samples of human infrarenal abdominal aortic aneurysm (AAA) and 5 samples of normal aorta (NA), all resected in operation, and 5 samples of primary hepatocellular carcinoma. Northern blot was used to evaluate the expression of heparanase. Immunohistochemistry and computer assisted image analysis were used to assess the expression of heparanase and its substrate heparan sulfate proteoglycan protein (HSGP) and microvessel hyperplasia. Results Semi quantitative analysis showed that the expression of heparanase in AAA was significantly higher than that in normal abdominal aorta ( P <0.01), but equivalent to that in primary hepatocellular carcinoma ( P >0.05). However, the expression of HSPG was lowered in AAA and was significantly negatively correlated with the expression of heparanase and microvessel density. Both of heparanase and HSPG were mainly located in adventitia and intima of AAA walls. Conclusion Heparanase participates in the structure damage and remodeling of abdominal aorta at matrix level, which contributes to AAA formation.