Accumulated evidence has manifested that long noncoding RNA (lncRNA) is involved in the progress of Parkinson's disease (PD). SNHG7, a novel lncRNA, has been found to be involved in tumorigenesis. However, SNHG7 expression and its functional effects on PD remain uncharted. Rotenone (Rot) was adopted to construct PD models in Sprague-Dawley (SD) rats and SH-SY5Y cells, respectively. The expression levels of caspase 3, tyrosine hydroxylase (TH), ionized calcium-binding adapter molecule 1 (Iba1) in SD rat striatum were measured via immunohistochemistry and western blot. Additionally, the expressions of inflammatory cytokines (interleukin 1β [IL-1β], IL-6, tumor necrosis factor α) and oxidative stress factors (malondialdehyde, superoxide dismutase, and glutathione peroxidase) in the brain tissues were examined using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Moreover, the protein levels of tumor necrosis factor receptor-associated factor (TRAF5), I-κB, nuclear factor-κB (NF-κB), HO-1, Nrf2 were detected via western blot. Bioinformatics was applied to predict the targeting relationship between SNHG7, miR-425-5p, and TRAF5. Dual-luciferase activity assay and RNA immunoprecipitation assays were conducted to verify their interactions. In comparison to healthy donors, SNHG7 was found upregulated while miR-425-5p expression was downregulated in PD patients. Functional experiments confirmed that SNHG7 downregulation or miR-425-5p overexpression attenuated neuronal apoptosis in the Rot-mediated PD model, TH-positive cell loss, and microglial activation by mitigating inflammation and oxidative stress. Mechanistically, SNHG7 served as a competitive endogenous RNA by sponging miR-425-5p and promoted TRAF5 mediated inflammation and oxidative stress. Inhibition of SNHG7 ameliorated neuronal apoptosis in PD through relieving miR-425-5p/TRAF5/NF-κB signaling pathway modulated inflammation and oxidative stress, and similar results were observed in the Rot-mediated rat model of PD.

中文翻译：

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长链非编码 RNA SNHG7 的下调通过靶向 miR-425-5p/TRAF5/NF-κB 轴来保护帕金森病模型中的炎症和细胞凋亡

积累的证据表明，长链非编码RNA（lncRNA）与帕金森病（PD）的进展有关。SNHG7 是一种新的 lncRNA，被发现与肿瘤发生有关。然而，SNHG7 的表达及其对 PD 的功能影响仍然未知。分别采用鱼藤酮（Rot）在Sprague-Dawley（SD）大鼠和SH-SY5Y细胞中构建PD模型。通过免疫组织化学和蛋白质印迹法测定 SD 大鼠纹状体中半胱天冬酶 3、酪氨酸羟化酶 (TH)、离子化钙结合衔接分子 1 (Iba1) 的表达水平。此外，炎症细胞因子（白细胞介素 1β [IL-1β]、IL-6、肿瘤坏死因子 α）和氧化应激因子（丙二醛、超氧化物歧化酶、分别使用实时聚合酶链反应和酶联免疫吸附试验检测脑组织中的谷胱甘肽过氧化物酶和谷胱甘肽过氧化物酶。此外，通过蛋白质印迹检测肿瘤坏死因子受体相关因子（TRAF5）、I-κB、核因子-κB（NF-κB）、HO-1、Nrf2的蛋白水平。应用生物信息学预测SNHG7、miR-425-5p和TRAF5之间的靶向关系。进行双荧光素酶活性测定和 RNA 免疫沉淀测定以验证它们的相互作用。与健康供体相比，在 PD 患者中发现 SNHG7 上调，而 miR-425-5p 表达下调。功能实验证实 SNHG7 下调或 miR-425-5p 过表达减弱 Rot 介导的 PD 模型中的神经元凋亡、TH 阳性细胞丢失、通过减轻炎症和氧化应激激活小胶质细胞。从机制上讲，SNHG7 通过海绵化 miR-425-5p 作为竞争性内源性 RNA 并促进 TRAF5 介导的炎症和氧化应激。抑制 SNHG7 通过缓解 miR-425-5p/TRAF5/NF-κB 信号通路调节炎症和氧化应激来改善 PD 中的神经元凋亡，并且在 Rot 介导的 PD 大鼠模型中观察到类似的结果。