CADASIL是Notch3基因突变导致的一种最常见的遗传性脑小血管病，主要病理改变是微小动脉的平滑肌细胞发育障碍和变性，伴随细胞外Notch3蛋白聚集形成颗粒样嗜锇物质，平滑肌细胞出现内质网应激，伴随线粒体相互联系减少、数量增加以及结构异常和氧自由基的产生增加，提示线粒体和内质网均被累及。我们在患者皮肤微小动脉观察到该病的典型血管病理改变，本研究对CADASIL患者的皮肤微小动脉平滑肌细胞采取免疫双标记方法在共聚焦显微镜下观察内质网和线粒体二者的空间关系；观察内质网应激相关蛋白以及自噬相关蛋白的改变；突变Notch3基因转染并培养血管平滑肌细胞，采取超氧炫技术分析培养细胞的线粒体渗透性转换孔的功能状态以及超氧自由基产生规律，预期确定Notch3基因突变是否通过干扰内质网线粒体复合体功能导致平滑肌细胞的发育障碍和变性，为该病的治疗提供新的理论依据。

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is an inherited small-vessel disease caused by mutations in Notch3 gene. Degeneration of vascular smooth muscle cells and deposition of GOM composed of Notch3 protein on the cell surface are the main pathological changes. The cultured vascular smooth muscle cells showed endoplasmic reticulum stress, increase of free radical formation with loss of mitochondrial connection and irregular structures, increase of mitochondrial numbers. The cutaneous arterioles in CADASIL presented typical vasculopathy of this disease, which confirmed by our studies.in present project we use the techniques of Confocal Laser Scanning Microscopy we study the connection of mitochondria and endoplasmic reticulum, the endoplasmic address and autophagy related porteins. Mutated Notch3 gene transfect the vascular smooth muscle cells， the superoxide flashes to study the level of OFR. Our findings will provide new insight into understanding the role of mitochondria-endoplasmic reticulum in the phathogenesis of vascular smooth muscle cells of CADASIL disease. This will help us to find new therapeutic strategies for this disease.