小胶质细胞介导的中枢炎症反应在帕金森病（PD）进展中起关键作用，然而小胶质细胞的活化机制尚不明确。LncRNA与miRNA是神经退行性病变和免疫炎症反应的重要调控因子，我们前期研究发现，lincRNA-p21作为p53的下游效应分子，与miR-181b-5p/PKC-δ相互作用，促进小胶质细胞的活化。因此，根据ceRNA理论，本课题拟从分子、细胞、动物模型水平证明lincRNA-p21作为ceRNA，竞争性“吸附”miR-181b-5p，间接上调PKC-δ，同时PKC-δ又促进p53/lincRNA-p21的表达，彼此形成一正反馈环路协同促进小胶质细胞的活化，加剧PD进展；同时我们将在临床水平对lincRNA-p21与PD发病、分级、药物疗效进行相关性分析。该研究不仅可以丰富现有对PD分子生物学机制的认识，为PD药物治疗提供新的靶点，也有望发掘PD临床诊断和疗效评价的量化指标。

The role of microglia mediated neuroinflammation in the progression of Parkinson's disease (PD) is well established, but the regulatory mechanism of microglial activation is still not clear. Many studies show that both lncRNA and miRNA are important regulatory factors in neurodegenerative disease and immune inflammation, our previous study showed that lincRNA-p21 served as a repressor in p53-dependent transcriptional responses, and promoted the activation of microglial cells, with the mutual regulation of miR-181b-5p and PKC-δ. Therefore, according to the "competing endogenous RNA(ceRNA)" theory put forward in recent years, this study intends to verify that lincRNA-p21 acts as a ceRNA, competitivly "sponges" miR-181b-5p, and indirectly up-regulates PKC-δ in molecular, cellular, and animal model levels. Moreover, as PKC-δ could promote the expression of p53, lincRNA-p21 forms a double-negative feedback loop with miR-181b-5p/PKC-δ and promotes the activation of microglia synergistically, which deteriorates the development of PD. We are also going to explore the correlation of lincRNA-p21 with the onset, grade, and drug efficacy of PD in clinical level. Our study might clarify the role of lincRNA-p21-mediated micraglial activation in the progression of PD, therefore contribute to the present knowledge of PD molecular biology, provide new target for biological intervention of PD, and explore quantitative index of the clinical diagnosis and the therapeutic evaluation of PD.