中文摘要
帕金森病(PD)是中老年第二大神经变性疾病,其病理特征是黑质多巴胺能神经元变性缺失伴Lewy小体(LB)的形成。LB内主要有a-突触核蛋白 、泛素等。近来研究表明:LB形成与泛素-蛋白酶体系统(UPS)功能缺损密切相关,UPS是体内异常蛋白降解的重要通路;而蛋白加工、折叠、降解的调控又与内质网应激(ERS)有密切关系;炎症因子可激活ERS;UPS和ERS功能异常可导致细胞内异常蛋白的蓄积,甚至细胞死亡(凋亡)。中药独活为祛风湿类药,纵观历代医家记载,独活还具有调补五脏,尤善补肾,祛瘀化痰,宣通脑络功效。前期研究表明,独活香豆素能通过调节免疫功能、抗氧化损伤和兴奋性氨基酸谷氨酸毒性及降低黑质多巴胺能神经元的凋亡而改善Lactacystin诱导的PD模型大鼠行为学异常。本研究拟通过体内、外实验,观察祛风湿类中药对ESR、UPS及炎症因子、凋亡因子影响,探讨其保护多巴胺能神经元的可能机制。
英文摘要
Parkinson's disease(PD) is the second largest neurodegenerative disease in the middle-aged and its pathological characteristics are loss of dopaminergic neurons in the substantia nigra and whith formation of Lewy body (LB) .LB is mainly within a-Synuclein, ubiquitin protein. Recent research has shown that LB formation is closely related to the functional defect of ubiquitin proteasome system (UPS) , UPS is an important pathway of abnormal protein degradation in vivo;And regulations of protein processing, folding and degradation are closely related to Endoplasmic reticulum stress(ERS);Inflammatory cytokines can activate the ERS;UPS and ERS dysfunction can lead to the accumulation of abnormal proteins in cells and even cell death(apoptosis).Duhuo is a kind of wind -damp dispelling herbs .Throughtout the records of generations of doctors,it can tonify the five zang-organs, especially the kidney, dispelling static blood and phlegm, and dredging cerebral vascellum.Early research has shown that Duhuo coumarin could improve abnormal behavior of Lactacystin-induced PD model rats by regulating immune function and resisting ioxidative damage ,excitatory aminoacid glutamate toxicity and apoptosis of dopaminergic neurons in the substantia nigra.This research, through experiments in vivo and in vitro ,aims to observe the influence of the wind-damp dispelling herbs on ESR, UPS, inflammatory factors and apoptosis factors ,and to explore its possible mechanisms of protecting DA neurons.?????.
