放射性臂丛神经损伤性病变与致病因素的关联性及保护性干预研究

Radiation induced brachial plexus injury is one of the most serious complications during radiotheraphy for breast cancer and head and neck malignancies.However,there has been no clear mechanism and effective therapy for this serious complication so far .The applicant and his research group have established the rat model of radiation induced brachial plexus injury successfully and found that radiation can cause the injury of musculocutaneous nerve ,rimification of brachial plexus nerve ,and neuron apoptosis regulated by c-fos gene in their previous work by imitating radiotherapy scheme for breast cancer.Furthermore ,we will observe the pathological changes and regularity of the brachial plexus and its motoneuron,the fibrous tissue and blood vessels nearby after radiation by means of histology,immunohistochemistry ， RT-PCR ,genome-wide expression profiling determination ,and investigate the pathophysiology,developing regularity,screening differentially expressed genes ,and interacting relationship between possible main etiological factors .Then we will carry out research about the intervention and protection of radiation induced brachial plexus injury,aiming to provide new insights and theoretical basis for the early prophylaxis and therapy for this complication and guarantee important experimental basis for clinical application.

放射性臂丛神经损伤是放射治疗乳腺癌及头颈部恶性肿瘤的严重并发症之一。目前，该病的发病机制不明，且无有效的治疗方法。申请者及所在课题组前期工作通过模拟乳腺癌放疗方案，成功建立了放射性臂丛神经损伤的大鼠模型，研究发现射线可以引起臂丛神经分支-肌皮神经损伤及由c-fos基因调控的神经元凋亡。在此基础上，我们将采用组织学、免疫组化、 RT-PCR及全基因组表达谱测定等方法，观察射线照射后臂丛神经及其运动神经元、神经周围纤维组织及血管的病变特点及其时间规律，探讨臂丛神经照射后的病理生理过程、演变规律，筛查差异基因，以及可能的主要致病因素之间相互的关系，并在此基础上进行辐射引起臂丛神经损伤干预或保护的实验研究，为该病的早期防治提供新思路和理论基础，以及为临床应用提供重要的实验依据。

项目主要致力于放射性臂丛神经损伤的发病机制及有效的治疗方法的探寻。我们通过模拟乳腺癌放疗方案，成功建立了放射性臂丛神经损伤的大鼠模型。经研究发现射线可以引起臂丛神经分支-肌皮神经损伤及由c-fos基因调控的神经元凋亡。同时，我们采用组织学、免疫组化、 RT-PCR及全基因组表达谱测定等方法，观察射线照射后臂丛神经及其运动神经元、神经周围纤维组织及血管的病变特点及其时间规律，探讨臂丛神经照射后的病理生理过程、演变规律，筛查差异基因，以及可能的主要致病因素之间相互的关系，并在此基础上进行辐射引起臂丛神经损伤干预或保护的实验研究，确定甲强龙、γ-干扰素、神经生长因子和黄芪联合用药后对臂丛神经损伤的保护作用最强，为该病的早期防治提供了新思路和理论基础，为后继临床应用提供了重要的实验依据。