目的 探究银杏内酯B（ginkgolide B，GB）对帕金森病（Parkinson's disease，PD）模型大鼠的保护作用。 方法 采用脑内定位注射6-OHDA建立大鼠PD模型，随机分为Sham组、模型组、美多芭组（20 mg/kg）和GB低、中、高剂量组（15、30、60 mg/kg），另将大鼠随机分为Sham组、Model组、GB 60 mg/kg组、LY294002组和（GB 60 mg/kg+LY294002）组，旋转实验检测大鼠行为学，试剂盒检测MDA、SOD、GSH水平，ELISA检测IL-6、IL-1β、TNF-α水平，Western blot检测大鼠黑质和纹状体组织PI3K/Akt信号通路蛋白表达情况。 结果 治疗后，美多芭组和GB中、高剂量组大鼠旋转圈数明显少于模型组（P<0.05），MDA和IL-6、IL-1β、TNF-α水平明显低于模型组（P<0.05），SOD、GSH水平、p-PI3K、p-Akt蛋白表达明显高于模型组（P<0.05）；与LY294002组比较，（GB 60 mg/kg+LY294002）组大鼠p-PI3K、p-Akt蛋白表达明显上调（P<0.05），MDA和IL-6、IL-1β、TNF-α水平明显降低（P<0.05），SOD、GSH水平明显升高（P<0.05）。 结论 高剂量GB可改善PD大鼠行为学，增强抗氧化应激能力，减轻炎性损伤，起到一定保护作用，其机制可能与调节PI3K/Akt信号通路有关。
Abstract
Objective To explore the protective effects of ginkgolide B (GB) on model rats with Parkinson's disease (PD). Methods PD rat models were established by intracerebral injection of 6-OHDA, and they were randomly divided into a sham group, a model group, a Madopar group (20 mg/kg) and low-, middle- and high-dose GB groups (15, 30, 60 mg/kg). The rats were randomly divided into a Sham group, a Model group, a GB 60 mg/kg group, a LY294002 group and a GB 60 mg/kg+ LY294002 group, and rotating experiment was used to detect the behaviors of rats. Kit test was used to detect the levels of MDA, SOD and GSH, and ELISA was applied to measure the levels of IL-6, IL-1β and TNF-α. Western blot was applied to detect the expressions of PI3K/Akt signaling pathway proteins in rat substantia nigra and striatal tissue. Results After treatment, the number of rotations of rats in Madopar group and middle- and high-dose GB groups was significantly less than that in model group (P<0.05). The levels of MDA, IL-6, IL-1β and TNF-α were significantly lower than those in model group (P<0.05), while the levels of SOD, GSH and protein expressions of p-PI3K, p-Akt were significantly higher than those in model group (P<0.05). Compared with the LY294002 group, the protein expressions of p-PI3K and p-Akt significantly increased (P<0.05), and the levels of MDA and IL-6, IL-1β and TNF-α significantly reduced (P<0.05) while the levels of SOD and GSH significantly increased (P<0.05) in the GB 60 mg/kg+ LY294002 group. Conclusions High-dose GB can improve the behaviors of PD rats, enhance the ability of anti-oxidative stress, relieve inflammatory injury, and play a certain protective effect. In addition, its role mechanism may be related to the regulation of PI3K/Akt signaling pathway.
关键词
银杏内酯B /
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帕金森病 /
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神经功能 /
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PI3K/Akt信号通路
Key words
Ginkgolide B /
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Parkinson's disease /
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Neurological function /
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PI3K/Akt signaling pathway
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基金
淮安市自然科学研究计划类（HAB201843）
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