原人参三醇对亨廷顿病大鼠模型中3-硝基丙酸诱导的氧化应激具有保护作用。
Protopanaxtriol protects against 3-nitropropionic acid-induced oxidative stress in a rat model of Huntington's disease.
作者信息
Gao Yan, Chu Shi-feng, Li Jian-ping, Zhang Zhao, Yan Jia-qing, Wen Zhi-lin, Xia Cong-yuan, Mou Zheng, Wang Zhen-zhen, He Wen-bin, Guo Xiao-feng, Wei Gui-ning, Chen Nai-hong
机构信息
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Shanxi University of Traditional Chinese Medicine, Taiyuan 030024, China.
出版信息
Acta Pharmacol Sin. 2015 Mar;36(3):311-22. doi: 10.1038/aps.2014.107. Epub 2015 Feb 2.
AIM
Protopanaxtriol (Ppt) is extracted from Panax ginseng Mayer. In the present study, we investigated whether Ppt could protect against 3-nitropropionic acid (3-NP)-induced oxidative stress in a rat model of Huntington's disease (HD) and explored the mechanisms of action.
METHODS
Male SD rats were treated with 3-NP (20 mg/kg on d 1, and 15 mg/kg on d 2-5, ip). The rats received Ppt (5, 10, and 20 mg/kg, po) daily prior to 3-NP administration. Nimodipine (12 mg/kg, po) or N-acetyl cysteine (NAC, 100 mg/kg, po) was used as positive control drugs. The body weight and behavior were monitored within 5 d. Then the animals were sacrificed, neuronal damage in striatum was estimated using Nissl staining. Hsp70 expression was detected with immunohistochemistry. Reactive oxygen species (ROS) generation was measured using dihydroethidium (DHE) staining. The levels of components in the Nrf2 pathway were measured with immunohistochemistry and Western blotting.
RESULTS
3-NP resulted in a marked reduction in the body weight and locomotion activity accompanied by progressive striatal dysfunction. In striatum, 3-NP caused ROS generation mainly in neurons rather than in astrocytes and induced Hsp70 expression. Administration of Ppt significantly alleviated 3-NP-induced changes of body weight and behavior, decreased ROS production and restored antioxidant enzymes activities in striatum. Moreover, Ppt directly scavenged free radicals, increased Nrf2 entering nucleus, and the expression of its downstream products heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidase 1 (NQO1) in striatum. Similar effects were obtained with the positive control drugs nimodipine or NAC.
CONCLUSION
Ppt exerts a protective action against 3-NP-induced oxidative stress in the rat model of HD, which is associated with its anti-oxidant activity.
目的
原人参三醇（Ppt）从人参中提取。在本研究中，我们调查了Ppt是否能在亨廷顿舞蹈病（HD）大鼠模型中预防3 - 硝基丙酸（3 - NP）诱导的氧化应激，并探讨其作用机制。
方法
雄性SD大鼠腹腔注射3 - NP（第1天20 mg/kg，第2 - 5天15 mg/kg）。在给予3 - NP之前，大鼠每天口服Ppt（5、10和20 mg/kg）。尼莫地平（12 mg/kg，口服）或N - 乙酰半胱氨酸（NAC，100 mg/kg，口服）用作阳性对照药物。在5天内监测体重和行为。然后处死动物，用尼氏染色评估纹状体中的神经元损伤。用免疫组织化学检测Hsp70表达。用二氢乙锭（DHE）染色测量活性氧（ROS）生成。用免疫组织化学和蛋白质印迹法测量Nrf2途径中各组分的水平。
结果
3 - NP导致体重和运动活性显著降低，并伴有进行性纹状体功能障碍。在纹状体中，3 - NP主要在神经元而非星形胶质细胞中引起ROS生成并诱导Hsp70表达。给予Ppt可显著减轻3 - NP诱导的体重和行为变化，减少ROS产生并恢复纹状体中的抗氧化酶活性。此外，Ppt直接清除自由基，增加Nrf2进入细胞核，并增加其下游产物血红素加氧酶 - 1（HO - 1）和NAD（P）H醌氧化还原酶1（NQO1）在纹状体中的表达。阳性对照药物尼莫地平或NAC也有类似作用。
结论
Ppt在HD大鼠模型中对3 - NP诱导的氧化应激发挥保护作用，这与其抗氧化活性有关。
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