| 庞洪波,何晓非,张译文,等.α-倒捻子素对帕金森病小鼠的神经保护作用[J].安徽医药,2022,26(9):1710-1714. |
| α-倒捻子素对帕金森病小鼠的神经保护作用 |
| Neuroprotective effect of α-mangostin on Parkinson's disease in mice |
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| DOI：10.3969/j.issn.1009-6469.2022.09.004 |
| 中文关键词: 山竹子 α-倒捻子素 帕金森病 1-甲基-4-苯基-1，2，3，6-四氢吡啶 多巴胺 神经保护 小鼠，近交 C57BL |
| 英文关键词: Garcinia mangostana α-mangostin Parkinson's disease MPTP Dopamine Neuroprotection Mice, inbred C57BL |
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| 中文摘要: |
| 目的探讨α-倒捻子素对帕金森病小鼠的神经保护作用。方法2018年7月至2019年8月，将40只C57BL/6小鼠按随机数字表法分为四组，分别为对照组、模型组、α-倒捻子素给药组(低剂量组、高剂量组)，每组10只。模型组与α-倒捻子素给药组使用1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)诱导帕金森病小鼠模型。α-倒捻子素给药组分别给予5 mg1kg111d11、15mg1kg111d11的α-倒捻子素灌胃给药。给药后14 d，使用爬杆实验、转棒实验、悬挂实验观测小鼠的行为学表现；高压液相电化学技术测定纹状体多巴胺、高香草酸、3，4-二羟基苯乙酸(DOPAC)的含量；免疫荧光染色检测酪氨酸羟化酶(TH)表达；TUNEL染色检测细胞凋亡水平；蛋白质印迹法检测凋亡相关蛋白表达。结果与对照组(9.3±1.7)s、(205.8±31.3)s、(2.2±0.4)分、(2051.4±195.2)ng/g、(1 677.3±128.0)ng/g、(395.8±41.1)ng/g、(1.00±0.17)、(1.00±0.14)、(1.00±0.15)比较，模型组小鼠的爬杆时间(19.8±3.5)s升高，转棒停留时间(118.9±28.4)s和悬挂实验得分(1.0±0.3)分均降低；纹状体多巴胺(911.3±88.5)ng/g、高香草酸(11190.5±83.3)ng/g、DOPAC(187.9±20.3)ng/g含量降低；黑质区TH表达降低；黑质区细胞凋亡水平升高；黑质区B细胞淋巴瘤-2(Bcl-2)(0.23±0.11)表达量降低，Bcl-2相关X蛋白(Bax)(3.15±0.42)和活化胱天蛋白酶-9(cleaved-caspase-9)(4.27±0.52)表达量升高(P<0.05)。与模型组比较，低剂量组和高剂量组小鼠的爬杆时间［(15.4±3.1)s、(11.9±2.6)s］降低，转棒停留时间［(166.7±19.9)s、(192.1±21.5)s］和悬挂实验得分［(1.5±0.4)分、(1.9±0.6)分］均升高；纹状体多巴胺［(1 388.6±159.9)ng/g、(1728.2±180.6)ng/g］、高香草酸［(1 366.7±109.2)ng/g、(1 510.8±112.4)ng/g］、DOPAC［(266.5±33.7)ng/g、(320.3±40.4)ng/g］含量升高；黑质区TH表达升高；黑质区细胞凋亡水平降低；黑质区Bcl-2表达量［(0.44±0.19)、(0.94±0.22)］升高，Bax［(2.06±0.38)、(1.18±0.20)］和cleaved-caspase-9表达量［(2.29±0.43)、(1.30±0.28)］降低(P<0.05)。高剂量组的上述指标均优于低剂量组(P<0.05)。结论α-倒捻子素可以改善帕金森病小鼠的行为学表现，上调多巴胺及其代谢产物的含量，促进TH表达，抑制细胞凋亡水平。 |
| 英文摘要: |
| Objective To explore the neuroprotective effect of α-mangostin on Parkinson's disease (PD) in mice.Methods The starting and ending time of this study was from July 2018 to August 2019. Forty C57BL/6 mice were randomly assigned into four groups: control group, model group, α-mangostin administration group (low dose group and high dose group), there were 10 rats in each group. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to induce Parkinson's disease model in the model group and the α-mangostin administration group. The α-mangostin administration group was administered with 5 mg1kg111d11 and 15 mg1kg111d11 of α-mangostin by gavage. On the 14th day after administration, the behavior of mice was observed by climbing bar test, rotating bar test and hanging test. The contents of dopamine, homovanillic acid and 3,4-dihydroxyphenylacetic acid (DOPAC) in striatum were measured by high pressure liquid phase electrochemical technique. The expression of Tyrosine hydroxylase (TH) was detected by immunofluorescence staining; apoptosis level was detected by TUNEL staining. The expression of apoptosis-related protein was detected by Western blotting.Results Compared with the control group (9.3±1.7) s, (205.8±31.3) s, (2.2±0.4) points, (2 051.4±195.2) ng/g,(1 677.3±128.0) ng/g, (395.8±41.1) ng/g, (1.00±0.17), (1.00±0.14), (1.00±0.15), the climbing time (19.8±3.5) s of the mice in the model group was increased, the rod staying time (118.9±28.4) s and suspension test scores (1.0±0.3) points were decreased, the content of dopamine (911.3±88.5) ng/g, homovanillic acid, (11190.5±83.3) ng/g and DOPAC (187.9±20.3) ng/g in striatum were decreased, the expression of TH in substantia nigra was decreased, the level of cell apoptosis in substantia nigra was increased, the expression of B cell lymphoma-2 (Bcl-2) (0.23±0.11) was decreased and the expression of Bcl2-Associated X protein (Bax) (3.15±0.42) and cleaved-caspase-9 (4.27±0.52) were increased (P<0.05). Compared with the model group, the climbing time of the mice in the low-dose group and the high-dose group [(15.4±3.1) s, (11.9±2.6) s] was decreased, the rod staying time [(166.7±19.9) s, (192.1±21.5) s] and suspension test scores [(1.5±0.4) points, (1.9±0.6) points] were increased, the content of dopamine [(1 388.6±159.9) ng/g, (1 728.2±180.6) ng/g], homovanillic acid [(1 366.7±109.2) ng/g, (1 510.8±112.4) ng/g], DOPAC [(266.5±33.7) ng/g, (320.3±40.4) ng/g] were increased, the expression of TH was increased, the level of cell apoptosis in substantia nigra was decreased, the expression of Bcl-2 [(0.44±0.19), (0.94±0.22)] was increased and the expression of Bax [(2.06±0.38), (1.18±0.20)] and cleaved-caspase-9 [(2.29±0.43), (1.30±0.28)] were decreased(P<0.05). The above indicators in the high-dose group were better than those in the low-dose group (P<0.05).Conclusion α-mangostin can improve the behavior of MPTP induced Parkinson's disease mice, up-regulate the content of dopamine and its metabolites,promote the expression of TH, and inhibit the level of cell apoptosis. |
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