Maresin 1 promotes nerve regeneration and alleviates neuropathic pain after nerve injury.
Maresin 1 promotes nerve regeneration and alleviates neuropathic pain after nerve injury.
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Maresin 1 促进神经再生并减轻神经损伤后的神经性疼痛
DOI：
10.1186/s12974-022-02405-1
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发表时间：
2022-02-02
影响因子：
9.3
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Wei J;Su W;Zhao Y;Wei Z;Hua Y;Xue P;Zhu X;Chen Y;Chen G
周围神经损伤（PNI）是一个公共卫生问题，导致感觉和运动障碍以及神经性疼痛和继发性病变。目前，PNI的有效治疗方法仍然有限。例如，虽然神经生长因子（NGF）被广泛用于治疗PNI以促进神经再生，但它也会引起疼痛。Maresin 1（MaR 1）是一种抗炎和促分解介质，具有再生组织的潜力。我们确定MaR 1是否能够促进神经再生以及减轻神经病理性疼痛，并被认为是治疗PNI的假定治疗剂。用8周龄成年雄性ICR小鼠建立PNI模型，并通过局部应用、鞘内注射或足底注射给予NGF、MaR 1或生理盐水治疗。治疗后进行行为学分析和肌肉萎缩试验。采用免疫荧光法检测ATF-3、GFAP、IBA 1和NF 200的表达。采用实时荧光定量RT-PCR法检测炎症因子IL-1 β、IL-6和TNF-α的表达水平。通过蛋白质印迹分析检测AKT、ERK、mTOR、PI 3 K、磷酸化AKT、磷酸化ERK、磷酸化mTOR和磷酸化PI 3 K水平。全细胞膜片钳记录瞬时受体电位香草酸1（TRPV 1）电流。MaR 1在促进小鼠坐骨神经挤压损伤后感觉和运动功能恢复方面比NGF表现出更强的能力。免疫组织化学分析表明，MaR 1的管理与神经挤压损伤的小鼠减少受损的DRG神经元的数量，促进受损的神经再生和抑制腓肠肌萎缩。用MaR 1或从MaR 1处理的小鼠收集的DRG神经元培养的ND 7/23细胞的Western印迹分析显示，MaR 1通过PI 3 K-AKT-mTOR信号通路调节神经突生长。此外，MaR 1剂量依赖性地减轻神经损伤引起的机械异常性疼痛和热痛觉过敏。与镇痛作用一致，MaR 1抑制辣椒素引起的TRPV 1电流，抑制神经损伤诱导的脊髓小胶质细胞和星形胶质细胞的激活，并减少PNI小鼠脊髓背角中促炎细胞因子的产生。MaR 1对PNI小鼠的应用显着促进神经再生并减轻神经病理性疼痛，表明MaR 1是一种有前途的PNI治疗剂。在线版本包含补充材料，可通过10.1186/s12974-022-02405-1获得。
Peripheral nerve injury (PNI) is a public health concern that results in sensory and motor disorders as well as neuropathic pain and secondary lesions. Currently, effective treatments for PNI are still limited. For example, while nerve growth factor (NGF) is widely used in the treatment of PNI to promote nerve regeneration, it also induces pain. Maresin 1 (MaR1) is an anti-inflammatory and proresolving mediator that has the potential to regenerate tissue. We determined whether MaR1 is able to promote nerve regeneration as well as alleviating neuropathic pain, and to be considered as a putative therapeutic agent for treating PNI. PNI models were constructed with 8-week-old adult male ICR mice and treated with NGF, MaR1 or saline by local application, intrathecal injection or intraplantar injection. Behavioral analysis and muscle atrophy test were assessed after treatment. Immunofluorescence assay was performed to examine the expression of ATF-3, GFAP, IBA1, and NF200. The expression transcript levels of inflammatory factors IL1β, IL-6, and TNF-α were detected by quantitative real-time RT-PCR. AKT, ERK, mTOR, PI3K, phosphorylated AKT, phosphorylated ERK, phosphorylated mTOR, and phosphorylated PI3K levels were examined by western blot analysis. Whole-cell patch-clamp recordings were executed to detect transient receptor potential vanilloid 1 (TRPV1) currents. MaR1 demonstrated a more robust ability to promote sensory and motor function recovery in mice after sciatic nerve crush injury than NGF. Immunohistochemistry analyses showed that the administration of MaR1 to mice with nerve crush injury reduced the number of damaged DRG neurons, promoted injured nerve regeneration and inhibited gastrocnemius muscle atrophy. Western blot analysis of ND7/23 cells cultured with MaR1 or DRG neurons collected from MaR1 treated mice revealed that MaR1 regulated neurite outgrowth through the PI3K–AKT–mTOR signaling pathway. Moreover, MaR1 dose-dependently attenuated the mechanical allodynia and thermal hyperalgesia induced by nerve injury. Consistent with the analgesic effect, MaR1 inhibited capsaicin-elicited TRPV1 currents, repressed the nerve injury-induced activation of spinal microglia and astrocytes and reduced the production of proinflammatory cytokines in the spinal cord dorsal horn in PNI mice. Application of MaR1 to PNI mice significantly promoted nerve regeneration and alleviated neuropathic pain, suggesting that MaR1 is a promising therapeutic agent for PNI. The online version contains supplementary material available at 10.1186/s12974-022-02405-1.
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DOI：
10.1096/fj.202001145r
发表时间：
2020-10
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Huang R;Vi L;Zong X;Baht GS
通讯作者：
Baht GS
DOI：
10.4049/jimmunol.1600837
发表时间：
2016-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Colas RA;Dalli J;Chiang N;Vlasakov I;Sanger JM;Riley IR;Serhan CN
通讯作者：
Serhan CN
影响因子：
6
作者：
Jha MK;Jeon S;Suk K
通讯作者：
Suk K
影响因子：
14.5
作者：
Dong, Hai-Lin;Ma, Yin;Wu, Zhi-Ying
通讯作者：
Wu, Zhi-Ying
影响因子：
5.3
作者：
Francos-Quijorna, Isaac;Santos-Nogueira, Eva;Lopez-Vales, Ruben
通讯作者：
Lopez-Vales, Ruben