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。
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.
[1] Rasheed MZ, Andrabi SS, Salman M, et al. Melatonin improves behavioral and biochemical outcomes in a rotenone-induced rat model of Parkinson's disease[J]. J Environ Pathol Toxicol Oncol, 2018, 37(2): 139-150. DOI: 10.1615/JEnvironPatholToxicolOncol.2018025666.
[2] Jhao YT, Chiu CH, Chen CF, et al. The effect of Sertoli cells on Xenotransplantation and allotransplantation of ventral mesencephalic tissue in a rat model of Parkinson's disease[J]. Cells, 2019, 8(11): 1420-1441. DOI: 10.3390/cells8111420.
[3] 许侃, 胡光菊. 银杏叶提取物对老年血管性痴呆患者认知功能及血液流变学参数的影响[J]. 中南医学科学杂志, 2019, 47(6): 621-624. DOI: 10.15972/j.cnki.43-1509/r.2019.06.015.
[4] Yang XH, Zheng TZ, Hong H, et al. Neuroprotective effects of Ginkgo biloba extract and Ginkgolide B against oxygen-glucose deprivation/reoxygenation and glucose injury in a new in vitro multicellular network model[J]. Front Med, 2018, 12(3): 307-318. DOI: 10.1007/s11684-017-0547-2.
[5] Wu TT, Fang XY, Xu JH, et al. Synergistic effects of ginkgolide b and protocatechuic acid on the treatment of Parkinson's disease[J]. Molecules (Basel, Switzerland), 2020, 25(17): 3976-3989. DOI: 10.3390/molecules25173976.
[6] 张思妍, 王宝, 陶凯, 等. 帕金森病大鼠模型的建立及超声影像评价[J]. 中华超声影像学杂志, 2020, 29(6): 540-544. DOI: 10.3760/cma.j.cn131148-20191128-00738.
[7] 孔凡丛, 蔡莹, 杨燕. 左旋多巴诱导的异动症与突触后相关受体研究进展[J]. 中国临床实用医学, 2019, 10(6): 73-76. DOI: 10.3760/cma.j.issn.1673-8799.2019.06.019.
[8] 颜江. 补肾活血通络方剂对老年帕金森病痴呆患者认知功能,生活质量及脑脊液IL-6,IL-1β,TNF-α,IFN-γ水平的影响[J]. 现代中西医结合杂志, 2017, 26(27): 2983-2985, 3066. DOI: 10.3969/j.issn.1008-8849.2017.27.006.
[9] 张晓愉, 张昆鹏, 王建民, 等. 圣草次苷调控MPTP诱导的慢性小鼠帕金森疾病和机制研究[J]. 中国免疫学杂志, 2020, 36(3): 369-374. DOI: 10.3969/j.issn.1000-484X.2020.03.021.
[10] 王昆, 罗小娜, 李时光, 等. Nrf2/HO-1信号通路在6-羟基多巴胺帕金森病模型大鼠神经损伤中的作用[J]. 中国医药生物技术, 2019, 14(3) :237-244. DOI: 10.3969/j.issn.1673-713X.2019.03.007.
[11] 张辉, 马惠清, 王晓娟. 银杏叶提取物通过激活Nrf2-ARE信号通路对帕金森病大鼠发挥脑保护作用[J]. 沈阳药科大学学报, 2018, 271(8): 675-679. DOI: 10.14066/j.cnki.cn21-1349/r.2018.08.013.
[12] 刘星亮, 范磊, 宋征宇, 等. 银杏内酯B通过调控长链非编码RNA MALAT1的表达对MPP~+诱导SH-SY5Y细胞帕金森模型的保护作用[J]. 中药材, 2019, 42(6): 1413-1416. DOI: 10.13863/j.issn1001-4454.2019.06.041.
[13] Rai SN, Dilnashin H, Birla H, et al. The role of PI3K/Akt and ERK in neurodegenerative disorders[J]. Neurotox Res, 2019, 35(3): 775-795. DOI: 10.1007/s12640-019-0003-y.
[14]Gong J, Zhang L, Zhang Q, et al. Lentiviral vector-mediated SHC3 silencing exacerbates oxidative stress injury in nigral dopamine neurons by regulating the PI3K-AKT-FoxO signaling pathway in rats with Parkinson's disease[J]. Cell Physiol Biochem, 2018, 49(3): 971-984. DOI: 10.1159/000493228.
[15] Ji YF, Wang D, Zhang BA, et al. Bergenin ameliorates MPTP-induced Parkinson's disease by activating PI3K/Akt signaling pathway[J]. J Alzheimers Dis, 2019, 72(3): 823-833. DOI: 10.3233/JAD-190870.
京ICP备08002354号-3
