中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (7): 1333-1339.doi: 10.4103/1673-5374.272620

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

Exendin-4可通过减轻脊神经结扎模型大鼠海马神经炎症改善疼痛引起的认知障碍

  

  • 出版日期:2020-07-15 发布日期:2020-09-15

Exendin-4 attenuates pain-induced cognitive impairment by alleviating hippocampal neuroinflammation in a rat model of spinal nerve ligation

Shan-Shan Cui1 , Xiao-Bo Feng2 , Bing-Hong Zhang1 , Zhong-Yuan Xia1 , Li-Ying Zhan1, *   

  1. 1 Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China 2 Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China
  • Online:2020-07-15 Published:2020-09-15
  • Contact: Li-Ying Zhan, MD, PhD, 2582062108@qq.com.
  • Supported by:
    This study was supported by the Special Grant for Scientific and Technological Development Conducted by The Central Government of China in 2016: Quality Test and Operation with Anesthesia Center of Experimental Animal of Hubei Province, No. 2060403 (to BHZ).

摘要: orcid: 0000-0002-4828-0764 (Li-Ying Zhan)

Abstract: Glucagon-like peptide-1 receptor has anti-apoptotic, anti-inflammatory, and neuroprotective effects. It is now recognized that the occurrence and development of chronic pain are strongly associated with anti-inflammatory responses; however, it is not clear whether glucagon-like peptide-1 receptor regulates chronic pain via anti-inflammatory mechanisms. We explored the effects of glucagon-like peptide-1 receptor on nociception, cognition, and neuroinflammation in chronic pain. A rat model of chronic pain was established using left L5 spinal nerve ligation. The glucagon-like peptide-1 receptor agonist exendin-4 was intrathecally injected into rats from 10 to 21 days after spinal nerve ligation. Electrophysiological examinations showed that, after treatment with exendin-4, paw withdrawal frequency of the left limb was significantly reduced, and pain was relieved. In addition, in the Morris water maze test, escape latency increased and the time to reach the platform decreased following exendin-4 treatment. Immunohistochemical staining and western blot assays revealed an increase in the numbers of activated microglia and astrocytes in the dentate gyrus of rat hippocampus, as well as an increase in the expression of tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6. All of these effects could be reversed by exendin-4 treatment. These findings suggest that exendin-4 can alleviate pain-induced neuroinflammatory responses and promote the recovery of cognitive function via the glucagon-like peptide-1 receptor pathway. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Renmin Hospital of Wuhan University of China (approval No. WDRM 20171214) on September 22, 2017.

Key words: astrocyte, chronic pain, cognitive impairment, exendin-4, hippocampal dentate gyrus, microglia, Morris water maze, neuroinflammation, spinal nerve ligation