CADASIL皮肤活检中血管超微结构改变

目的报道12例伴皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病（CADASIL）患者的皮肤血管超微结构改变。方法12例患者分别来自4个不同的CADASIL家族，均以发作性头晕、头痛、缺血性脑卒中和痴呆为主要表现。基因检查证实Notch3基因存在突变。12例患者均做皮肤活检，16例同龄的非CADASIL患者作为对照，观察血管超微结构改变。结果12例患者的皮肤血管超微结构表现：大多数血管壁增厚，颗粒样嗜锇性物质主要沉积在小动脉和小静脉血管平滑肌细胞表面，偶尔位于毛细血管内皮细胞周围。血管平滑肌细胞和内皮细胞变性，它们细胞质中许多充满嗜锇性物质小泡以及线粒体空泡样变性。16例对照中仅1例老年人中偶见血管基底膜增厚。结论退行性变的血管平滑肌细胞和嗜锇颗粒（GOM）是CADASIL特征性病理改变。内皮细胞变性和线粒体改变也在CADASIL致病机理中占有重要作用。这些改变和Notch3基因突变之间的关系还需要扩大样本进一步确定。

Ultrastructural picture of blood vessels of skin biopsy in CADASIL

Objective To evaluate the vascular ultrastructural changes in 12 probands from different CADASIL families. Methods Skin biopsies were performed in 12 probands, who had the main sympotoms of dizziness, headache, recurrent stroke and dementia. The diagnosis was confirmed genetic results of Notch3 gene analyses in all probands. The skin biopsy specimens, including 12 patients and 16 non-CADASIL controls, were examined under electron microscopes. Results The vascular ultrastructural features in skin of 12 CADASIL patients were： In all probands, granular osmiophilic deposits（GOM） varied in size and shape, was noted in the basal lamina of Vascular smooth muscle cells （VSMCs）, more common affecting the arterioles and few, the capilaries and veins; degenerationl VSMCs and endothelial cells, with numerous osmiophilic pinocytotic vesi- cles and abnormal mitochondria; mild thickening of arteriole intima was observed in 1 control. Conclusions The pathological hallmark of the disease is major alterations of VSMCs and the presence of specific GOM. Im- paired endothelial function and mitochondria may play a role in the pathogenetic research of the CADASIL. The relationship both the extra-cerebral vascular ultrastructural changes and the Notch3 gene mutations need to be determined in the further.