Galectin-3抑制与神经性疼痛周围神经损伤后衰减
Zhicong Ma1,2☯, Qi Han3☯, Xiaolei Wang3☯, Zisheng Ai4, Yongjun Zheng3*　

　
　　摘要
　　神经性疼痛仍然是一个普遍和持久的临床问题,因为它通常是不适应当前使用止痛剂。非常迫切需要开发出新的药物来缓解神经性疼痛。Galectin-3 (gal3)是一种多功能蛋白属于汽车——bohydrate-ligand凝集素家族,由不同的细胞表达。新兴的研究表明gal3诱导出促炎症反应通过招募和激活lympho cytes,巨噬细胞和小胶质细胞。在这项研究中,我们调查是否gal3抑制会抑制周围神经损伤后神经炎症和缓解神经性疼痛。我们发现L5脊神经结扎(SNL)增加的表达在背根神经节gal3 mRNA和蛋白水平。鞘内管理修改柑橘果胶(MCP), gal3抑制剂,减少gal3表达式在背根神经节。

Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury
Zhicong Ma1,2☯, Qi Han3☯, Xiaolei Wang3☯, Zisheng Ai4, Yongjun Zheng3*
1 Department of Anesthesiology, The 2nd Hospital of Shanxi Medical University, Taiyuan, 030001, China,
2 Department of Anesthesiology, Xiangya Hospitalaffiliated to Central South University, Changsha 410008, China, 3 Department of Pain Management and Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital affiliated to Fudan University, No.221, West Yan'an Road, Shanghai, 200040, China,
4 Department of Preventive Medicine, College of Medicine, Tongji University, Shanghai 200092, China
☯ These authors contributed equally to this work.
* zhengyongjun1971@126.

Abstract
Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the car- bohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lympho- cytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin(MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autop- hagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory media- tors including IL-1β, TNF-α and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation.