中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (3): 454-459.doi: 10.4103/1673-5374.179058

• 原著:退行性病与再生 • 上一篇    下一篇

粉防己碱对血管性痴呆的神经保护

  

  • 收稿日期:2015-08-13 出版日期:2016-03-15 发布日期:2016-03-15
  • 基金资助:

    中国国家自然科学基金项目(81070886)

Neuroprotective effects of tetrandrine against vascular dementia

Yan-ling Lv 1, Ze-zhi Wu 2, Li-xue Chen 1, Bai-xue Wu 1, Lian-lian Chen 1, Guang-cheng Qin 1, Bei Gui 1, Ji-ying Zhou 1   

  1. 1 Laboratory Research Center, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
    2 Key Laboratory of Biorheological Science and Technology of the State Ministry of Education, College of Bioengineering, Chongqing
    University, Chongqing, China
  • Received:2015-08-13 Online:2016-03-15 Published:2016-03-15
  • Contact: Li-xue Chen, M.D.,chenlixue@163.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81070886.

摘要:

粉防己碱是防己科植物石蟾蜍的主要活性成分,对缺血性脑血管病具有确切的治疗效果,但其是否也能治疗血管性痴呆尚未能确定。实验通过双侧颈总动脉闭塞建立慢性血管性痴呆大鼠模型,8周后以10或30 mg/kg粉防己碱隔天腹腔注射,连续治疗4周后予以验证。HE染色和尼氏染色显示,大鼠海马活细胞百分率增加,神经元坏死减少,病理损伤减轻;Western blot显示大鼠海马白细胞介素1β表达减少,N甲基D天冬氨酸2B受体磷酸化减轻;水迷宫测试显示,大鼠延迟期缩短,在目标象限的游泳时间延长。结果表明,粉防己碱对慢性血管性痴呆通过降低白细胞介素1β表达,减少N甲基D天冬氨酸2B受体磷酸化,进而减少神经元坏死,而产生的神经保护作用。

关键词: 神经再生, 粉防己碱, 缺血性脑血管病, 血管性痴呆, 白细胞介素1β, N-甲基-D-天冬氨酸受体, N甲基D天冬氨酸2B受体-Tyr1472磷酸化, 神经元坏死

Abstract:

Tetrandrine is one of the major active ingredients in Menispermaceae Stephania tetrandra S. Moore, and has specific therapeutic effects in ischemic cerebrovascular disease. Its use in vascular dementia has not been studied fully. Here, we investigated whether tetrandrine would improve behavioral and cellular impairments in a two-vessel occlusion rat model of chronic vascular dementia. Eight weeks after model establishment, rats were injected intraperitoneally with 10 or 30 mg/kg tetrandrine every other day for 4 weeks. Behavioral assessment in the Morris water maze showed that model rats had longer escape latencies in training trials, and spent less time swimming in the target quadrant in probe trials, than sham-operated rats. However, rats that had received tetrandrine showed shorter escape latencies and longer target quadrant swimming time than untreated model rats. Hematoxylin-eosin and Nissl staining revealed less neuronal necrosis and pathological damage, and more living cells, in the hippocampus of rats treated with tetrandrine than in untreated model rats. Western blot assay showed that interleukin-1β expression, and phosphorylation of the N-methyl-D-aspartate 2B receptor at tyrosine 1472, were lower in model rats that received tetrandrine than in those that did not. The present findings suggest that tetrandrine may be neuroprotective in chronic vascular dementia by reducing interleukin-1β expression, N-methyl-D-aspartate receptor 2B phosphorylation at tyrosine 1472, and neuronal necrosis.

Key words: nerve regeneration, tetrandrine, ischemic cerebrovascular disease, vascular dementia, N-methyl-D-aspartic acid receptor 2B, ronal necrosis, neural regeneration