基质金属蛋白酶与Ⅳ型胶原在马方综合征并发胸主动脉瘤中表达的研究

Expression of matrix metalloproteinase and Ⅳ type collagen in thoracic aortic aneurysms with Marfan's syndrome

目的探讨基质金属蛋白酶MMP-2和金属蛋白酶组织抑制剂TIMP-2与Ⅳ型胶原在马方综合征(MS)并发的胸主动脉瘤中的表达及其意义。方法采用免疫组化SP法和伊红-苏木素(HE)染色技术分别检测10例马方综合征并发胸主动脉瘤患者血管壁病变中MMP-2蛋白和TIMP-2蛋白及Ⅳ胶原的表达水平和病理学形态改变。结果光镜下见MS并发胸主动脉瘤壁中的弹性纤维和胶原纤维有明显黏液样变性,囊性中膜坏死区(CMN)有大量的黏蛋白沉积。平滑肌细胞有变性、坏死。免疫组化见MMP-2蛋白在MS并发胸主动脉瘤壁病变区边缘的平滑肌细胞中呈强阳性表达,而在非病变区呈弱阳性表达,其表达强度显著高于非病变区。TIMP-2蛋白在MS并发胸主动脉瘤壁病变区和非病变区的平滑肌细胞中均呈弱阳性表达,两者的表达强度无明显差异。Ⅳ型胶原在胸主动脉瘤壁的病变区呈阴性表达,而在非病变区呈阳性表达。结论基质金属蛋白酶MMP-2的过度分泌、激活,TIMP-2的活性降低与马方综合征并发胸主动脉瘤壁中的弹性纤维及胶原纤维黏液样变性密切相关。MMP-2,TIMP-2和Ⅳ型胶原在马方综合征并发的胸主动脉瘤的发生发展中起一定的作用。

[Objective] To determine the expression lever of matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-2 and Ⅳ type collagen in thoracic aortic aneurysms of patients with Marfan＇s syndrome and their significance in the pathogenesis of aortic aneurysms. [Methods]Tile morphologic changes of thoracic aortic a- neurysms from 10 patiens with Marfan＇s syndrome were analysised by HE staining. The expressions MMP-2 and TIMP-2 protein, and type Ⅳ collagen were determined by immunohistochemistry method . [Results] The medial of aortic aneurysms showed extensive myxoid degeneration of elastic and collagen fibers under microscopy.Plenty of myxoid substance was accumulated in the region of cystic medial necrosie （CMN）, and disruption as well as necrosis of smooth muscle cells was also observed. A characteristic finding was that the expression of MMP-2 at the border of CMN was stronger than that in other areas, while the expression of TIMP-2 showed lower expresson both in CMN and no-pathological areas. Negative expression of type Ⅳ collagen in CMN but positive expression of that in nopathological areas respectively were found. [Conclusion] Overexpression and activation of MMP-2 protein, accompanying with the down expression of TIMP-2 protein ,was associated with myxoid degeneration of elastic and collagen in thoracic aorta caused by Marian＇s syndrome. MMP-2, T/MP-1 and type Ⅳ collagen protein play an important role in the development of thoracic aortic aneurysms related to Marfan＇s syndrome.