退行性变主动脉瓣的组织病理学特点及其发生机制

Histopathologic features of degenerative aortic valve and its mechanisms

目的探讨退行性变主动脉三叶瓣的组织病理学特点及其发生机制。方法收集2009年5月至2010年5月在天津胸科医院心外科因主动脉瓣狭窄行手术切除的严重钙化的主动脉三叶瓣标本22例[男14例，女8例，年龄（66-t-6）岁]和因夹层动脉瘤行Bentall手术的正常三叶式主动脉瓣标本6例[男4例，女2例，年龄（43±5）岁]。经HE染色和免疫组织化学染色，观察退行性主动脉瓣的病理组织学改变，通过其病理特征的改变了解参与主动脉瓣退行性变的相关机制。结果狭窄的主动脉瓣瓣叶增厚，瓣叶主动脉侧出现钙化灶；主动脉瓣内膜下有炎细胞浸润、新生毛细血管、胆固醇结晶和泡沫样细胞聚集及弥漫性和结节性钙化灶。成骨相关转录因子（OSX）和活化T细胞核因子1（NFATcl）在正常主动脉瓣膜无阳性表达，而在病变瓣膜中则显示细胞核阳性表达。病变瓣膜OSX免疫组化0、1、2、3级表达在钙化部位分别为1例（4．5％）、1例（4．5％）、8例（36．4％）、12例（54．5％），在非钙化部位分别为4例（18．2％）、6例（27．3％）、7例（31．8％）、5例（22．7％）；NFATcl免疫组化0、1、2、3级表达在钙化部位分别为1例（4．5％）、1例（4．5％）、8例（36．4％）、12例（54．5％），在非钙化部位分别为4例（18．2％）、6例（27．3％）、8例（36．4％）、4例（18．2％）；钙化部位OSX和NFATcl的表达均高于非钙化部位（x。=8．320、P=0．040和x^2=9．371、P=0．025）。结论与正常瓣膜不同，病变瓣膜中出现了炎细胞浸润、脂质沉积、新生血管及骨调控因子的表达。

Objective To explore the related pathogenesis of degenerative aortic valvular disease by observing the histopathological changes of aortic valves from patients with aortic degenerative stenosis and compare the results with those controls with normal aortic valves. Methods Between May 2009 and May 2010, 22 cases of degenerative calcified aortic valves from patients with aortic valve stenosis undergoing aortic valve replacement （14 males, 8 females, mean age： （66 ＋_ 6） years） and 6 cases of normal aortic valves from those with dissection undergoing Bentall operation （4 males, 2 females, mean age： （43 ＋_ 5 ） years） were collected. The results of hematoxylin and eosin staining and immunohistochemical examinations were used to observe the histological features of degenerative aortic valves and elucidate the related pathogenesis of degenerative aortic valvuar disease. Results Degenerative aortic valve leaflets became thickened. Calcification appeared in aortic side of valve leaflets. Inflammatory infiltrate, angiogenesis, cholesterol crystals, foamy cell aggregation, diffuse and nodular calcification could be seen in subendocardial space of degenerative aortic valve leaflets. No expression of Osterix （OSX） or nuclear factor of activated T- cells 1 （ NFATel ） was observed in normal valves. In contrast, the expressions of OSX and NFATcl showed nuclear immunostaining in degenerative aortic valves. Immunohistochemical staining was graded from 0 to 3. And the expression of OSX was present in 1 （4. 5% ）, 1 （4. 5% ）, 8 （36. 4% ） and 12 cases （54. 5% ） respectively in calcified areas, that of OSX in 4（ 18.2% ）, 6（27.3% ）, 7（31.8% ） and 5 cases （22. 7% ） respectively in non-calcified areas, that of NFATcl in 1 （4. 5% ）, 1 （4. 5% ）, 8 （36. 4% ） and 12 cases （54. 5% ） respectively in calcified areas, that of NFATcl in 4 （ 18. 2% ）, 6 （ 27. 3% ）, 8 （ 36.4% ） and4 cases （ 18.2% ） respectively in non-calcified areas. The expressions of OSX and NFATcl in calcified areas were higher than those in non-calcified areas （ X^2 = 8. 320, P = 0. 040 and X^2 = 9. 371, P = 0. 025 respectively ） . Conclusions Unlike in normal valves, inflammatory infiltrate, lipid deposition, angiogenesis and bone regulatory factors appear in degenerative aortic valves. And inflammatory infiltrate, lipid deposition, angiogenesis and ossification may be involved in the degenerative calcified aortic stenosis.