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七叶皂苷钠调控SIRT1/NF-κB信号通路对帕金森病大鼠的神经保护作用
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| 篇名： | 七叶皂苷钠调控SIRT1/NF-κB信号通路对帕金森病大鼠的神经保护作用 |
| TITLE： | Neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating SIRT1/NF-κB signaling pathway |
| 摘要： | 目的 探究七叶皂苷钠通过调控沉默信息调节因子1（SIRT1）/核因子κB（NF-κB）信号通路发挥对帕金森病大鼠的神经保护作用。方法采用6-羟基多巴胺注射法构建帕金森病大鼠模型，将建模成功的48只大鼠随机分为模型组、七叶皂苷钠低剂量组（1.8mg/kg）、七叶皂苷钠高剂量组（3.6mg/kg）、七叶皂苷钠+EX527组（七叶皂苷钠3.6mg/kg+SIRT1抑制剂EX5275mg/kg），每组12只；另取12只健康大鼠作为假手术组。各药物组大鼠腹腔注射相应药液，每天1次，持续21d。末次给药结束24h后，检测大鼠运动及认知功能，观察其黑质区和海马组织CA1区神经元形态，检测其黑质纹状体中多巴胺（DA）含量和黑质区酪氨酸羟化酶（TH）、α突触核蛋白（α-Syn）表达水平，检测其血清中促炎因子[白细胞介素6（IL-6）、IL-18]、抗炎因子（IL-10）水平及黑质纹状体中SIRT1、磷酸化NF-κBp65（p-NF-κBp65）、NF-κBp65蛋白表达水平。结果与假手术组比较，模型组大鼠黑质区和海马组织CA1区神经元损伤严重；其旋转圈数、逃避潜伏期、黑质区α-Syn蛋白表达水平、血清中促炎因子水平、黑质纹状体中p-NF-κBp65与NF-κBp65蛋白的相对表达量之比均显著升高或延长（P＜0.05），目标象限停留时间、黑质纹状体中DA含量及黑质区TH蛋白表达水平、血清中抗炎因子水平、黑质纹状体中SIRT1蛋白表达水平均显著缩短或降低（P＜0.05）。与模型组比较，七叶皂苷钠各剂量组大鼠神经元损伤程度减轻，各定量指标均显著改善，且高剂量组的改善更为明显（P＜0.05），而EX527可逆转高剂量七叶皂苷钠的改善作用（P＜0.05）。结论七叶皂苷钠可通过上调SIRT1蛋白表达来抑制NF-κB信号激活，从而抑制帕金森病大鼠的神经炎症，改善其运动及认知功能障碍，最终起到神经保护作用。 |
| ABSTRACT： | OBJECTIVE To explore the neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating the silent information regulator 1 （SIRT1）/nuclear factor-κB （NF-κB） signaling pathway. METHODS The Parkinson’s disease rat model was constructed by using 6-hydroxydopamine injection method. Forty-eight rats successfully modeled were randomly divided into model group， sodium aescinate low-dose group （1.8 mg/kg）， sodium aescinate high-dose group （3.6 mg/kg）， sodium aescinate+EX527 （sodium aescinate 3.6 mg/kg+SIRT1 inhibitor EX527 5 mg/kg） group， with 12 rats in each group. Another 12 healthy rats were selected as the sham operation group. Each group was injected with the corresponding drug solution intraperitoneally， once a day， for 21 consecutive days. Twenty-four hours after the end of the last administration， the motor and cognitive functions of rats were detected， and the morphology of neurons in the substantia nigra and CA1 region of hippocampal tissue were observed. The content of dopamine （DA） in the nigrostriatal and the expression levels of tyrosine hydroxylase （TH） and α-synuclein （α-Syn） in the substantia nigra were detected. The serum levels of pro-inflammatory factor [interleukin-6 （IL-6）， IL-18]， anti-inflammatory factor （IL-10）， and the expression levels of SIRT1， phosphorylated NF-κB p65 （p-NF-κB p65） and NF- κB p65 protein in nigrostriatal were detected. RESULTS Compared with sham operation group， the neurons in the substantia nigra and CA1 region of hippocampal tissue were seriously damaged in model group； the number of rotations， escape latency， the expression levels of α-Syn in substantia nigra， the levels of serum pro-inflammatory factors， the relative expression ratio of p-NF- κB p65 and NF-κB p65 protein in nigrostriatal were increased or prolonged significantly （P＜0.05）； the target quadrant residence time， the content of DA in nigrostriatal， the expression level of TH in substantia nigra， the serum level of anti-inflammatory factor， and the expression level of SIRT1 protein in substantia nigra striatum were significantly decreased or shortened （P＜0.05）. Compared with model group， the damage degrees of neuron in sodium aescinate groups were alleviated， and the quantitative indicators were significantly improved， which were more significant in the high-dose group （P＜0.05）； EX527 could reverse the improvement effect of high-dose sodium aescinate （P＜0.05）. CONCLUSIONS Sodium aescinate can inhibit the activation of NF-κB signal by up-regulating the protein expression of SIRT1， thereby reducing the neuroinflammation of rats with Parkinson’s disease， improving the motor and cognitive dysfunctions， and finally playing a neuroprotective role. |
| 期刊： | 2024年第35卷第06期 |
| 作者： | 周慧敏；陈静；欧诒丹；王御林；钟纯正 |
| AUTHORS： | ZHOU Huimin，CHEN Jing，OU Yidan，WANG Yulin，ZHONG Chunzheng |
| 关键字： | 七叶皂苷钠；帕金森病；沉默信息调节因子1/核因子κB信号通路；运动功能；认知功能；炎症反应；神经保护 |
| KEYWORDS： | sodium aescinate； Parkinson’s disease； SIRT1/NF-κB signaling pathway； motor function； cognitive function； |
| 阅读数： | 27 次 |
| 本月下载数： | 10 次 |
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