I型神经纤维瘤病相关致病基因突变及其致病机理研究

Type I neurofibromatosis (NF1) is a common diseases in plastic surgery , meanwhile is one of the most common autosomal dominant genetic disease. The malignant transformation rate in late was up to 20%, and the clinical treatment is palliative resection only. utilization the advantage of genetic resources in our country, we intend to detect mutations in genes in several NF1 family, and discuss the relationship between the genotype and phenotype in NF1 gene, so as to to elucidate the function of the NF1 gene; Through the RNAi technology, we established stable NF1 gene silence of the rat SW10 immortalized schwann cell lines, and at the same time, the primary schwann cells originning from neurofibromatosis of NF1 patients were cultured, subsequently detected the correlation between NF1 gene inactivation and reactive oxygen species (ROS) , furthermore detect the change of the cell factors in Ras and ROS path respectively. Further to explore the correlation between the pathogenesis of NF1 and reactive oxygen species (ROS) . At the first time we used antioxidant in nude mouse neurofibromatosis model of experimental treatment. The study is to clarify neurofibromatosis molecular mechanism, to provide the experimental basis for the clinical application of antioxidant, and the employment in treatment will be the gospel of the NF1 patients.

I 型神经纤维瘤病（NF1）是整形外科常见的皮肤肿瘤疾病，是最常见的常染色体显性遗传病之一。晚期恶变率高达20%，目前临床治疗以姑息性切除为主。利用我国的遗传资源优势，我们拟通过对多个NF1家系致病基因突变的检测，探讨NF1基因型和表现型的关系，进一步阐明NF1基因的功能；通过RNAi技术，建立稳定沉默NF1基因的大鼠SW10永生化雪旺细胞系，同时原代培养源自患者神经纤维瘤的雪旺细胞，检测NF1基因失活与活性氧产物（ROS）的相关性，进一步研究Ras和ROS通路中有关细胞因子的变化。探讨NF1发病机制与活性氧产物（ROS）作用的相关性。首次将抗氧化剂用于裸鼠神经纤维瘤病模型的实验性治疗。该研究为阐明神经纤维瘤病的分子机制和防治提供了实验依据，而抗氧化剂的临床应用更将会是NF1患者的福音。