| 杨琪,李芳芳.丁苯酞通过调控TLR4/NF-κB信号通路保护帕金森病模型大鼠脑内黑质多巴胺能神经元.[J].中南医学科学杂志.,2024,(6):896-901. |
| 丁苯酞通过调控TLR4/NF-κB信号通路保护帕金森病模型大鼠脑内黑质多巴胺能神经元 |
| Dibenzophenone protects dopaminergic neurons in the substantia nigra of Parkinson's disease model rats by regulating the TLR4/NF-κB signaling pathway |
| 投稿时间：2024-05-13 修订日期：2024-10-15 |
| DOI：10.15972/j.cnki.43-1509/r.2024.06.005 |
| 中文关键词: 丁苯酞 帕金森病 TLR4/NF-κB 小胶质细胞活化 多巴胺能神经元 |
| 英文关键词:butylphthalide Parkinson's disease TLR4/NF-κB activation of microglia dopaminergic neurons |
| 基金项目:松滋市自然科学发展项目(SZ2023ZR086) 作者简介:杨琪,副主任医师,研究方向为脑血管疾病的诊治,E-mail为yq78628@qq.com。通信作者李芳芳,硕士,主治医师,研究方向为脑血管疾病的诊治,E-mail为249974843@qq.com。 |
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| 中文摘要: |
| 目的探讨丁苯酞通过调控Toll样受体4(TLR4)/核因子-κB(NF-κB)信号通路对帕金森病(PD)模型大鼠脑内黑质多巴胺能神经元的影响。 方法取SD大鼠48只,随机均分为假手术组、模型组、丁苯酞组、奥卡宁组。颈部注射鱼藤酮建立PD模型,造模成功后各组连续给药8周。观察大鼠行为学变化,检测大鼠神经元丢失及小胶质细胞活化情况,分析大鼠脑组织中神经细胞标志蛋白及炎症因子表达水平。取大鼠黑质多巴胺能神经元细胞系PC12,随机均分为对照组、模型组、丁苯酞组、ad-TLR4组、ad-NC组、丁苯酞+ad-TLR4组,用低剂量鱼藤酮模拟体外PD模型。比较各组多巴胺能神经元细胞损伤、凋亡状况及炎症因子水平、TLR4/NF-κB通路相关蛋白表达水平。 结果丁苯酞干预治疗及阻断TLR4/NF-κB通路,可缓解PD大鼠多巴胺能神经元丢失及小胶质细胞活化,抑制TLR4在小胶质细胞中表达(P＜0.05)。丁苯酞干预能显著抑制体外培养的多巴胺能神经元损伤及凋亡,抑制TLR4/NF-κB通路介导的免疫炎症反应(P＜0.05)。ad-TLR4可逆转丁苯酞的上述作用(P＜0.05)。 结论丁苯酞可能通过抑制TLR4/NF-κB通路激活,降低小胶质细胞活化介导的免疫炎症反应,缓解PD大鼠黑质多巴胺能神经元丢失。 |
| 英文摘要: |
| AimTo investigate the protective effects of butylphthalide on dopaminergic neuron damage in Parkinson’s disease (PD) rats by regulating the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) immune inflammatory pathway. MethodsForty-eight SD rats were taken and randomly divided into sham operation group, model group, butylphthalide group, and Okanin group by random number table, with twelve per group. Rotenone was injected into the neck to establish a PD model. After that the model was successfully established, the administration was continued for 8 weeks in each group. The behavioral changes of rats were observed. The loss of neurons and activation of microglia were detected. The expression levels of nerve cell marker proteins and inflammatory factors in rat brain were analyzed. The rat substantia nigra dopaminergic neuron cell line PC12 were taken and set as the control group, model group, butylphthalide group, ad-TLR4 group, ad-NC group, butylphthalide＋ad-TLR4 group, and low-dose rotenone was used to simulate an in vitro PD model. The injury and apoptosis of dopaminergic neurons, the level of neuronal inflammatory factors and the expression of TLR4/NF-κB pathway were compared among all groups. ResultsButylphthalide intervention and blocking the TLR4/NF-κB pathway could alleviate the loss of dopaminergic neurons and the activation of microglia in PD rats, and inhibit the expression of TLR4 in microglia (P＜0.05). Butylphthalide intervention could significantly inhibit the damage and apoptosis of dopaminergic neurons cultured in vitro, and inhibit the immune inflammatory response mediated by the TLR4/NF-κB pathway (P＜0.05). Ad-TLR4 could reverse the above effects of butylphthalide (P＜0.05). ConclusionButylphthalide may inhibit the activation of TLR4/NF-κB pathway, reduce the immune inflammatory response mediated by microglia activation, and alleviate the loss of substantia nigra dopaminergic neurons in PD rats. |
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