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中国临床药理学与治疗学 ›› 2024, Vol. 29 ›› Issue (5): 554-560.doi: 10.12092/j.issn.1009-2501.2024.05.010

• 基础研究 • 上一篇    下一篇

甘草苷抑制吗啡引起的神经损伤作用及机制

张建新,杨孝来   

  1. 甘肃省人民医院药剂科,兰州  730000,甘肃
  • 收稿日期:2023-08-04 修回日期:2023-10-24 出版日期:2024-05-26 发布日期:2024-04-16
  • 通讯作者: 杨孝来,男,教授,硕士生导师,研究方向:神经药理学。 E-mail: yxl1668@vip.163.com
  • 作者简介:张建新,男,主管药师,研究方向:神经药理学。 E-mail: gjjx1209@126.com
  • 基金资助:
    甘肃省青年科技基金计划项目(1506RJYA170)

Glycyrrhizin inhibits the neurotoxic effects and mechanisms induced by morphine

ZHANG Jianxin, YANG Xiaolai   

  1. Department of Pharmacy, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu, China 
  • Received:2023-08-04 Revised:2023-10-24 Online:2024-05-26 Published:2024-04-16

摘要:

目的:探讨甘草苷对吗啡引起神经损伤的调节作用及机制。方法:采用侧脑室注射吗啡建立神经损伤模型;腹腔注射甘草苷5 d和10 d,采用病理学观察、蛋白免疫印迹、细胞活力、凋亡及原代神经元分化检测。结果:吗啡处理之后,皮层组织中神经元减少,原代神经元细胞相对活力下降,凋亡数目增加,轴突断裂和胞体缩小;甘草苷给药后,细胞活力显著改善;轴突、树突及胞体结构逐渐完整,细胞凋亡情况减轻;蛋白Akt在473位点和PKA在197位点的磷酸化水平下降,自噬相关蛋白Becline和LC3B1/2不变。结论:甘草苷显著抑制吗啡引起的神经元分化抑制和神经元凋亡,这些作用可能是通过甘草苷协同吗啡对Akt通路。

关键词: 甘草苷, 吗啡, 细胞凋亡, 神经元分化

Abstract:

AIM: To investigate the regulatory effects and mechanisms of glycyrrhizin on morphine-induced neurotoxicity. METHODS: A neurotoxicity model was established by intracerebroventricular injection of morphine. Glycyrrhizin was administered intraperitoneally for 5 and 10 days. Pathological observation, protein immunoblotting, cell viability, apoptosis, and primary neuron differentiation were assessed. RESULTS: After morphine treatment, neuronal loss, decreased cell viability, increased apoptosis, axonal breakage, and cell shrinkage were observed in cortical tissue. Glycyrrhizin administration significantly improved cell viability, and axonal, dendritic, and cell body structures gradually became intact, with reduced apoptosis. The phosphorylation levels of protein Akt at position 473 and PKA at position 197 decreased, while autophagy-related proteins Beclin and LC3B1/2 remained unchanged. CONCLUSION: Glycyrrhizin significantly inhibits morphine-induced neuronal differentiation suppression and neuronal apoptosis, which may be mediated through the synergistic effects of glycyrrhizin and morphine on the Akt pathway. 

Key words: glycyrrhizin, morphine, cell apoptosis, neuronal differentiation

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