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近年来诸多证据显示,中枢神经统的免疫异常和炎症反应参与了黑质多巴胺能神经元的变性坏死。小胶质细胞的激活是脑内炎症反应的主要标志,小胶质细胞主要组织相容性复合物Ⅱ(MHCⅡ)的表达是小胶质细胞活化的标志。尽管人脑中的小胶质细胞并不持续表达MHCⅡ类分子,但随着年老以及在中枢神经系统出现病变的情况下(包括神经变性),它们的表达确是明显上调的。研究发现,在PD病人和PD动物模型的中脑黑质均可发现大量MHCⅡ阳性的小胶质细胞,MHCⅡ类分子在小胶质细胞将外源性抗原呈递给CD4+Th细胞的过程中起重要作用。在6-羟多巴胺(6-OHDA)、脂多糖(LPS)大鼠模型的观察发现,促红细胞生成素、地塞米松等能明显降低MHCⅡ的表达和小胶质细胞的活化,从而减轻动物模型的临床症状。鉴于MHCⅡ抗原启动的免疫反应在PD的发病过程中有促进慢性神经变性进展的作用,因此,抑制小胶质细胞活性和MHCⅡ表达对控制PD进展可能有重要的治疗上的意义。
In recent years, a lot of evidence shows that central nervous system immune abnormalities and inflammatory reactions involved in nigral dopaminergic neurons degeneration and necrosis. Activation of microglia is a major marker of inflammatory response in the brain. Expression of microglial major histocompatibility complex II (MHC II) is a marker of microglial activation. Although microglia in the human brain do not consistently express MHC class II molecules, their expression is indeed significantly up-regulated with aging and with lesions in the central nervous system, including neurodegeneration. The study found that a large number of MHC II-positive microglia can be found in substantia nigra of PD patients and PD animal models, and MHC class II molecules play an important role in microglial presentation of exogenous antigens to CD4 + Th cells Important role. In 6-OHDA and LPS rat models, we found that erythropoietin and dexamethasone can significantly reduce the expression of MHC Ⅱ and the activation of microglia, thus reducing the animal model The clinical symptoms. In view of MHC Ⅱ antigen-initiated immune response in the pathogenesis of PD have a role in promoting the progression of chronic neurodegenerative, therefore, inhibition of microglial activity and MHC Ⅱ expression may have important therapeutic significance in the control of PD progression.