目前临床上针对慢性缺血性脑白质病变尚无非常有效的治疗手段，因此很有必要阐明其发病机制。课题组在前期工作中首次发现在慢性脑缺血早期脑白质区域及向白质迁移的少突胶质前体细胞（OPC）明显增多，并且少突胶质细胞发生自噬和丢失，同时小胶质细胞高表达IL-1 beta。预实验还发现早期给予IL-1受体拮抗剂（IL-1Ra）可以明显减轻慢性缺血后脑白质损伤程度，改善认知功能，提示IL-1 beta在慢性缺血性脑白质病变早期可能发挥了重要作用，但其具体作用机制尚不清楚。本课题将利用IL-1受体1基因敲除小鼠及RNA干扰等手段，着重研究IL-1 beta在慢性缺血性脑白质病变早期的作用，包括对OPC迁移的抑制作用和机制，及对少突胶质细胞自噬性损伤的作用，同时评价IL-1Ra在慢性缺血性脑白质病变早期的治疗作用。本研究将为阐明慢性缺血性脑白质病变的发病机制提供更多理论基础，并为早期防治提供新的靶点和途径。

Chronic ischemic cerebral white matter disease is a common neurologic injury, which will induce white matter rarefaction, myelin impairment and dementia. In clinical therapy, until now there are no effective agents to reverse the chronic ischemic cerebral white matter disease or to prevent its progression, so it is very necessary to elucidate its pathogenesis. In the preliminary experiment, we for the first time found that the oligodendrocyte progenitor cell (OPC) in the white matter and the migrating OPC increased, but the oligodendrocyte lost with the occurrence of autophagy at the early phase of chronic ischemic cerebral white matter disease, meanwhile, the expression of IL-1beta upregulated. Moreover, administration of IL-1 receptor selective antagonist (IL-1Ra) obviously alleviated the chronic ischemic cerebral white matter lesions and the cognitive impairment, which suggests that IL-1beta plays an important role in the early phase of chronic ischemic cerebral white matter disease. However, its detailed mechanism is quite unclear. This project will investigate the effect of IL-1beta on chronic ischemic cerebral white matter disease and the involved mechanism as inhibiting the migration of OPC and promoting the autophagy in oligodendrocyte to induce its injury by using the IL-1 receptor 1 knock-out mice and RNA interference. Moreover, the effect of IL-1Ra on chronic ischemic cerebral white matter disease will also be evaluated. This project will give more evidence to elucidate the pathogenesis and supply new target to prevent or treat the chronic ischemic cerebral white matter disease.