中文摘要
帕金森病(PD)表现为黑质致密区多巴胺能神经元变性坏死伴胞浆内嗜酸性包涵体- - 路易小体的形成,路易小体的主要成分是α-突触核蛋白(α-syn),α-syn异常聚集可引起内质网应激(ERS),ERS在PD发病过程起重要作用。基于此思路,本课题拟在前期研究工作基础上,采用皮下注射鱼藤酮法制备大鼠PD模型,运用针刺风府、太冲进行治疗,研究ERS在鱼藤酮诱导的PD模型大鼠多巴胺能神经元损伤中的作用,ERS初期的未折叠蛋白反应(UPR),以及时间过长的ERS诱发的细胞凋亡在多巴胺能神经元的变性丢失中的调控机制。初步揭示针刺治疗PD的作用机制,可能是通过调节内质网应激,一方面激活UPR途径以重建内质网稳态,一方面抵抗细胞凋亡,从而发挥对多巴胺能神经元的保护和促进修复作用。确定针刺是保护多巴胺能神经元形态及功能免受损伤的有效方法,为针灸临床更有效防治PD提供可靠实验依据。
英文摘要
Dopaminergic degeneration and necrosis of neuron and the formation of Lewy body are the typical pathological features of Parkinson's disease. The main components of Lewy body is α-synuclein(α-syn).The abnormal aggregation of α-syn can cause endoplasmic reticulum stress(ERS). ERS plays an important role in the pathogenesis of PD. Based on this idea, we will carry out the research on the basis of the preliminary work with preparation of PD model by subcutaneous injection of rotenone method, using acupuncture Fengfu, Taichong therapy to research on ERS neuron injury in PD rats dopamine induced by rotenone, the unfolded protein response(UPR)of the early ERS and the regulation mechanism of ERS induced prolonged cell apoptosis in the degeneration of dopaminergic neurons loss. Maybe the mechanism of acupuncture in the treatment of PD is regulation via endoplasmic reticulum stress. On one hand, activation of the UPR pathway in the endoplasmic reticulum homeostasis reconstruction, On the other hand against apoptosis, so as to protect the dopaminergic neurons and promote repair. This research will provide reliable experimental basis for more effective prevention of PD in clinical acupuncture and moxibustion.
