| 吴王芳,周蓉靖,刘美真,等.牡荆苷对帕金森病大鼠的神经保护作用及AMPK/PGC-1α通路的影响[J].浙江中医药大学学报,2023,47(7):722-729. |
| 牡荆苷对帕金森病大鼠的神经保护作用及AMPK/PGC-1α通路的影响 |
| Neuroprotective Effect of Vitexin on Parkinson’s Disease Rats and the Effect on AMPK/PGC-1α Pathway |
| DOI：10.16466/j.issn1005-5509.2023.07.003 |
| 中文关键词: 牡荆苷 帕金森病 AMPK/PGC-1α 行为学 氧化应激 活性氧 神经保护 |
| 英文关键词: vitexin Parkinson’s disease AMPK/PGC-1α behavior oxidative stress ROS neuroprotection |
| 基金项目:2021年度宁波市医学科技计划项目(2021Y23)；第一批宁波市名中医药专家传承工作室建设项目宁波市李淑云名中医药专家传承工作室(甬卫发〔2022〕54号) |
|
| 摘要点击次数: 1322 |
| 全文下载次数: 698 |
| 中文摘要: |
| [目的] 探讨牡荆苷(Vitexin，Vit)对帕金森病(Parkinson’s disease，PD)大鼠的神经保护作用及其可能机制。[方法] 30只SD大鼠随机分为对照(normal control，NC)组、模型组和Vit低、中、高剂量(10、20、40 mg·kg-1)组，除NC组外均使用6-羟基多巴胺(6-hydroxydopamine，6-OHDA)诱导制备PD大鼠模型，模型组大鼠腹腔注射0.9%氯化钠溶液，牡荆苷各剂量组按照相应剂量腹腔注射给药。以阿朴吗啡(apomorphine，APO)诱导转圈，采用Catwalk步态分析行为学改变，免疫组化染色评估大鼠黑质酪氨酸羟化酶(tyrosine hydroxylase，TH)表达变化，同时检测大鼠大脑组织氧化应激指标超氧化物歧化酶(superoxide dismutase，SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase，GSH-Px)活性，丙二醛(malondialdehyde，MDA)和谷胱甘肽(glutathione，GSH)水平，免疫印迹检测大鼠腺苷酸活化蛋白激酶/过氧化物酶体增殖物激活受体γ共激活因子-1α(adenylate activated protein kinase/peroxlsome proliferator-activated receptor-γ coactivator-1α，AMPK/PGC-1α)通路相关蛋白表达水平。[结果] 与NC组比较，模型组体质量增加减少、食物转化效率(food conversion efficiency，FCE)降低(均P<0.05)，而转圈行为显著增加(P<0.01)，步态功能(速度、步幅、步频、站立时间)显著损害(均P<0.01)。与模型组比较，Vit各剂量组大鼠体质量增长及FCE增高(均P<0.05)，大鼠转圈行为减少(均P<0.05)，步态功能均有逆转(均P<0.05)，Vit高剂量组作用效果更明显(均P<0.05)。与NC组比较，模型组多巴胺能神经元标志物TH显著降低(P<0.01)；与模型组比较，Vit各剂量组黑质TH水平均显著升高(P<0.01)，且呈剂量依赖性，组间差异明显(P<0.05)。与NC组比较，模型组MDA水平增加(P<0.05)，GSH水平和GSH-Px、SOD活性降低(均P<0.05)，沉默信息调节因子1(silence information regulator 1，SIRT1)、PGC-1α、线粒体转录因子A(mitochondrial transcription factor A，TFAM)和核呼吸因子1(nuclear respiratory factor 1，NRF1)和磷酸化AMPK(phospho-adenylate activated protein kinase，p-AMPK)Th172蛋白表达均降低(均P<0.001)，而Vit中、高剂量组上述指标水平得到逆转(P<0.01，P<0.001)。[结论] Vit可能通过AMPK/PGC1α信号通路保护黑质多巴胺能神经元，调节氧化应激反应，进一步改善PD大鼠行为学和步态功能。 |
| 英文摘要: |
| [Objective] To investigate the neuroprotective effect of Vitexin(Vit) on Parkinson’s disease(PD) rats and its possible mechanism. [Methods] Thirty SD rats were randomly divided into normal control(NC) group， model group and low， middle and high dose(10，20，40 mg·kg-1) Vit groups. Except for NC group， PD rats were induced by 6-hydroxydopamine(6-OHDA). Intraperitonelly 0.9% sodium chloride solution was used in model group， and Vit in each dose group was given according to the corresponding dose of intraperitoneal injection. Apomorphine(APO) induced circle and Catwalk gait analysis behavior change， immunohistochemical staining were used to evaluate the changes of tyrosine hydroxylase(TH) in substantia nigra of rats， the activity of oxidative stress indexes superoxide dismutase(SOD)， glutathione peroxidase(GSH-Px); the levels of malondialdehyde(MDA) and glutathione(GSH) in brain tissue were detected， and the expression levels of proteins related to adenylate activated protein kinase(AMPK)/peroxlsome proliferator-activated receptor-γ coactivator-1α(PGC-1α) pathway were detected by Western blot. [Results] Compared with NC group， the body weight and food conversion efficiency(FCE) were decreased(P<0.05)， while the circle behavior was significantly increased(P<0.01) and gait function(speed， stride length， step frequency and standing time) was impaired in model group(P<0.01). Compared with model group， the body weight and FCE were increased in each Vit dose group(P<0.05)， while the circle behavior was decreased(P<0.05) and gait function was reversed(P<0.05). The effect of Vit-H was more obvious(P<0.05). Compared with NC group， dopaminergic neuron marker TH was significantly decreased in model group(P<0.01). Compared with model group， TH was significantly increased in each Vit dose group(P<0.01)， and it was dose-dependent in each group(P<0.05). Compared with NC group， MDA level was increased(P<0.05)， while GSH level， GSH-Px and SOD activity were decreased in model group(P<0.05)， silence information regulator 1(SIRT1)， PGC-1α， mitochondrial transcription factor A(TFAM) and nuclear respiratory factor 1(NRF1) and phospho-adenylate activated protein kinase(p-AMPK) Th172 protein expression were decreased in model group(P<0.001)， which were reversed in Vit-M and Vit-H group(P<0.01， P<0.001). [Conclusion] Vit may protect dopaminergic neurons in substantia nigra through AMPK/PGC-1α signaling pathway， regulate oxidative stress response， and further improve the behavior and gait function of PD rats. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
| 关闭 |