中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (14): 1395-1401.doi: 10.4103/1673-5374.137595

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

高表达的热休克蛋白72能抑制视网膜神经节细胞和外侧膝状体神经元凋亡

  

  • 收稿日期:2014-06-28 出版日期:2014-07-25 发布日期:2014-07-25

Heat shock protein 72 confers protection in  retinal ganglion cells and lateral geniculate nucleus neurons via blockade of the SAPK/JNK pathway in a chronic ocular-hypertensive rat model

Ning Li 1, Yuehua Li 2, Xuanchu Duan 2   

  1. 1 Department of Ophthalmology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
    2 Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
  • Received:2014-06-28 Online:2014-07-25 Published:2014-07-25
  • Contact: Xuanchu Duan, M.D., Ph.D., Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China, duanxchu@126.com.

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摘要：

单侧视神经切断会引起外侧膝状体区热休克蛋白72的高表达，说明热休克蛋白72可能参与神经元的抗损伤过程。鉴于硫酸锌和槲皮素分别能诱导和抑制热休克蛋白72的表达，实验设计了分别腹腔注射硫酸锌、JNK抑制剂SP600125和槲皮素于慢性高眼压大鼠模型中，并设损伤对照组对比。结果发现，与损伤对照组相比，硫酸锌注射组大鼠视网膜神经节细胞和外膝体神经元的热休克蛋白72表达升高，但槲皮素注射组热休克蛋白72表达降低。在干预后第3天，损伤对照组视网膜组织和外膝体神经元p-JNK和p-c-jun基因有表达，第7天达到高峰。干预后第7-28天，硫酸锌注射组和JNK抑制剂SP600125组外侧膝状体及视网膜组织p-c-jun表达显著下降，而槲皮素注射组p-c-jun蛋白的表达显著增加。结果说明，热休克蛋白72可能通过阻断SAPK/JNK凋亡通路的活化，减轻慢性高眼压大鼠模型视网膜神经节细胞和外侧膝状体神经元凋亡，以此发挥神经保护作用。

关键词: 神经再生, 周围神经损伤, 青光眼, 热休克蛋白72, 视网膜神经节细胞, 外侧膝状体, 硫酸锌, 槲皮素, SAPK/JNK通路, 神经保护, p-JNK；p-c-jun, 国家自然科学基金

Abstract:

Optic nerve transection increased the expression of heat shock protein 72 (HSP72) in the lateral geniculate body, indicating that this protein is involved in the prevention of neuronal injury. Zinc sulfate and quercetin induced and inhibited the expression of HSP72, respectively. Intraperitoneal injections of zinc sulfate, SP600125 (c-Jun N-terminal kinase inhibitor), or quercetin were performed on retinal ganglion cells in a Wistar rat model of chronic ocular hypertension. Our results showed that compared with the control group, the expression of HSP72 in retinal ganglion cells and the lateral geniculate body was increased after the injection of zinc sulfate, but was decreased after the injection of quercetin. The expression of phosphorylated c-Jun N-terminal kinases and phosphorylated c-Jun were visible 3 days after injection in the control group, and reached a peak at 7 days. Zinc sulfate and SP600125 significantly decreased the expression of p-c-Jun, whereas quercetin significantly enhanced the expression of this protein. These results suggest that HSP72 protects retinal ganglion cells and lateral geniculate body in a rat model of chronic ocular hypertension from injury by blocking the activation of the stress-activated kinase/c-Jun N-terminal kinase apoptotic pathway.

Key words: nerve regeneration, peripheral nerve injury, glaucoma, heat shock protein 72, retinal ganglion cells, lateral geniculate body, zinc sulfate, quercetin, SAPK/JNK pathway, neuroprotection, p-JNK, p-c-Jun, NSFC grant, neural regeneration