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长链非编码RNA TUG1在帕金森病中的作用及其对小胶质细胞炎症反应的影响

The Role of lncRNA TUG1 in the Parkinson Disease and Its Effect on Microglial Inflammatory Response.

作者信息

Cheng Jiang, Duan Yangyang, Zhang Fengting, Shi Jin, Li Hui, Wang Feng, Li Haining

机构信息

Department of Neurology, General Hospital of Ningxia Medical University, Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, NO.804 Shengli Street, Xingqing District, Yinchuan, 750004, Ningxia, China.

School of Clinical Medicine, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.

出版信息

Neuromolecular Med. 2021 Jun;23(2):327-334. doi: 10.1007/s12017-020-08626-y. Epub 2020 Oct 21.

DOI:10.1007/s12017-020-08626-y
PMID:33085068
Abstract

Parkinson's disease (PD) is a common neurodegenerative disease in the middle-aged and elderly populations. The purpose of this study was to investigate the clinical value of lncRNA TUG1 in PD and its effect on the microglial inflammatory response. A total of 181 subjects were recruited for the study, including 97 patients with PD (male/female 50/47) and 84 healthy individuals (male/female 41/43). There was no significant difference for gender and age distribution between the groups. The expression of serum TUG1 was determined by qRT-PCR. The receiver operating curve (ROC) was applied for diagnostic value analysis. CCK-8 was used to detect the effect of TUG1 on the proliferation of BV2 cells. The motor coordination ability of mice was tested by the rotarod and pole tests. ELISA was used to detect serum pro-inflammatory factors. TUG1 was highly expressed in the serum of PD patients. Serum TUG1 can distinguish PD patients to form healthy controls with the AUC of 0.902. Serum TUG1 was positively correlated with the levels of UPDRS, IL-6, IL-1β, and TNF-α in PD patients. Cell experiment results showed that the downregulation of TUG1 significantly inhibited cell proliferation and the release of TNF-α, IL-6, and IL-1β. Besides, animal experiments suggested that the downregulation of TUG1 significantly improved the motor coordination ability of the PD mice and inhibited the expression of inflammatory factors. lncRNA TUG1 is a latent biomarker of PD patients. TUG1 downregulation may inhibit the inflammatory response in the progression of PD. These findings provide a possible target for the early diagnosis and therapeutic intervention of PD.

摘要

帕金森病(PD)是中老年人群中常见的神经退行性疾病。本研究旨在探讨长链非编码RNA TUG1在帕金森病中的临床价值及其对小胶质细胞炎症反应的影响。本研究共纳入181名受试者,包括97例帕金森病患者(男/女50/47)和84名健康个体(男/女41/43)。两组间性别和年龄分布无显著差异。采用qRT-PCR检测血清TUG1的表达。应用受试者工作特征曲线(ROC)进行诊断价值分析。采用CCK-8检测TUG1对BV2细胞增殖的影响。通过转棒试验和杆试验检测小鼠的运动协调能力。采用ELISA检测血清促炎因子。TUG1在帕金森病患者血清中高表达。血清TUG1能够区分帕金森病患者和健康对照,曲线下面积(AUC)为0.902。帕金森病患者血清TUG1与统一帕金森病评定量表(UPDRS)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)水平呈正相关。细胞实验结果显示,TUG1下调显著抑制细胞增殖以及TNF-α、IL-6和IL-1β的释放。此外,动物实验表明,TUG1下调显著改善帕金森病小鼠的运动协调能力并抑制炎症因子的表达。长链非编码RNA TUG1是帕金森病患者潜在的生物标志物。TUG1下调可能抑制帕金森病进展中的炎症反应。这些发现为帕金森病的早期诊断和治疗干预提供了一个可能的靶点。

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