Differential expression of matrix structural proteins in cerebrovascular malformations

doi:10.3969/j.issn.2095-4344.2014.24.003

Abstract

Abstract:

BACKGROUND: Studies have shown that the wall structure matrix protein expression has some differences in brain vascular malformations, but the difference between the structure matrix proteins of vascular malformations and the correlation between structural protein difference and vascular malformations are rarely reported.
OBJECTIVE: To evaluate the differential expression of matrix structural proteins in vascular malformations of the brain.
METHODS: Fifty surgical specimens of cerebral vascular malformation and 34 normal specimens of superficial temporal artery were subject to hematoxylin-eosin staining. Single/polyclonal antibodies, produced by Santa Cruz, USA against four structural proteins matrix (IV collagen, a-smooth muscle protein, laminin, fibronectin) were applied for immunohistochemical staining.
RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that, cerebral vascular malformations showed significant disorder and constitute heteromorphism compared with normal vascular wall structure; in vascular malformations, there were obvious differences in cerebral arteriovenous malformations and cavernous hemangioma structure. Immunohistochemical staining showed that, in the normal temporal artery and vascular
malformations, IV collagen and smooth muscle actin-a were both positively expressed, and the positive rate had no difference, but the differences were significant in the structural arrangement. Laminin and fibronectin expression rate showed statistically significant differences between normal temporal artery and vascular malformations (P < 0.05), normal vascular wall expressed more laminin, while vascular malformations expressed more fibronectin. Laminin and fibronectin expression rate also had significant differences between cerebral arteriovenous malformation and cavernous hemangioma (P < 0.05), cerebral arteriovenous malformation expressed more laminin, while cavernous hemangioma expressed more fibronectin. The results confirmed that, compared with normal cerebral vessels, cerebral vascular malformations’ wall structure appears obvious heteromorphism, IV collagen and smooth muscle actin-a have apparent structural disorder, with low expression of laminin and high expression fibronectin, this difference may be the cause of abnormal cerebral wall structure.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

全文链接：

Key words: intracranial arteriovenous malformations, hemangioma, cavernous, extracellular matrix proteins, tissue engineering

CLC Number:

R318

Yang Zhen-cun, Wang Zeng-liang, Dang Mu-ren, Lin Ling-chao, Serick Duysenb. Differential expression of matrix structural proteins in cerebrovascular malformations[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(24): 3785-3790.

Figures/Tables 2

2.1 受试者数量分析此次研究中的研究对象为病理标本，所有标本均纳入结果分析，无脱落。 2.2 受试者基线分析脑血管畸形患者50例中男23例，女27例，平均年龄36岁。首发症状为脑出血36例，癫痫8例，头痛5例，局部神经功能障碍1例。所有患者均在发病3 d内完善检查并行手术取得标本。脑血管畸形多在青年人中发生，男女比例无明显差异，主要的首发症状为脑出血，病程无明显差异。正常血管组与畸形血管组及畸形血管组内的动静脉畸形组和海绵状血管瘤组患者的年龄、性别和病程差异无显著性意义(P > 0.05)，具有可比性。 2.3 脑血管畸形患者和正常人脑血管形态正常血管内膜层、肌层和外膜层结构紧密，层次分明，排列规则。动静脉畸形血管内膜疏松，平滑肌层结构排列紊乱，平滑肌间和外膜见胶原纤维沉积。海绵状血管瘤血管内膜层紊乱，未见明显平滑肌层，被大量胶原纤维代替，并见胶原玻璃样变性。苏木精-伊红染色显示，畸形血管与正常血管相比显现明显异形性，且海绵状血管瘤的血管壁结构组成异常更明显。见图1。 2.4 脑血管畸形患者和正常人脑血管组织中Ⅳ型胶原蛋白、a-血管平滑肌蛋白、层粘连蛋白和纤维连接蛋白的表达 Ⅳ型胶原蛋白在正常血管壁中均表达(+)，位于内皮细胞下层；在动静脉畸形中的表达均(+)，位于内皮细胞下层和血管中层；在海绵状血管瘤中表达均(+)，位于海绵间腔内、内皮细胞下层。正常血管和畸形血管Ⅳ型胶原蛋白染色阳性率均为100%，其阳性率差异比较无显著性意义(P > 0.05)。Ⅳ型胶原蛋白在畸形血管中全部阳性表达，但结构紊乱，排列不齐，管壁厚薄不均，与正常血管相比结构排列差异明显。畸形血管中海绵状血管瘤较脑动静脉畸形血管Ⅳ型胶原排列更加紊乱，结构异形性更加明显。见图2。 a-平滑肌肌动蛋白在正常血管壁中均表达(+)，位于内皮细胞下层；在动静脉畸形中的表达均(+)，位于内皮细胞下层和血管中层；在海绵状血管瘤中表达均(+)，位于海绵间腔内、内皮细胞下层。正常血管和畸形血管a-平滑肌肌动蛋白染色阳性率均为100%，其阳性率差异比较差异无显著性意义(P > 0.05)。a-平滑肌肌动蛋白在畸形血管中全部阳性表达，但a-平滑肌肌动蛋白结构不规则，排列疏松不均匀，与正常血管相比结构排列差异明显。畸形血管中海绵状血管瘤a-平滑肌肌动蛋白染色不明显，仅于内膜下层线性染色，且排列疏松不连续，较脑动静脉畸形血管异形性更明显。见图3。纤维连接蛋白在正常血管中表达1例呈(+)32例呈(-)，阳性率为1/34(3%)，分布内膜细胞下层；在动静脉畸形中表达10例呈(+)20例呈(-)，阳性率为10/30(33%)，分布内皮细胞层和内膜细胞下层；在海绵状血管瘤中表达19例呈(++)1例呈(-)，阳性率为19/20(95%)，分布于血管壁全层。畸形血管与正常血管比较纤维连接蛋白染色阳性率差异有显著性意义(P < 0.05)，畸形血管纤维连接蛋白染色更加明显；畸形血管中脑动静脉畸形和海绵状血管瘤间纤维连接蛋白染色阳性率差异也有显著性意义(P < 0.05)，海绵状血管瘤血管表达更多的纤维连接蛋白基质。见图4。层粘连蛋白在正常血管壁中表达均为(+)，阳性率为100%，分布内膜下层；在动静脉畸形中的表达20例呈(+)10例呈(-)，阳性率为20/30(67%)，分布内膜下层；在海绵状血管瘤中表达3例呈(+)17例呈(-)，阳性率为3/20(15%)，分布内膜下层。血管畸形与正常血管比较层粘连蛋白染色阳性率差异有显著性意义(P < 0.05)，正常血管层粘连蛋白染色更加明显；畸形血管中脑动静脉畸形和海绵状血管瘤间层粘连蛋白染色阳性率差异也有显著性意义(P < 0.05)，脑动静脉畸形血管表达更多的层粘连蛋白基质。见图5。"

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