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神经炎症在中枢神经系统中的扩散以小胶质细胞激活                             [ 5 ]  WANG D,ZHENG Y J,XIE J J,et al. Andrographolide
          为基础,小胶质细胞可在神经损伤后立即被激活,来促                                 inhibits the activation of spinal microglia and ameliorates
          进促炎因子IL-1β、IL-6和TNF-α大量释放,从而增强中                          mechanical allodynia[J]. Metab Brain Dis,2024,39(1):
          枢敏感性并诱发疼痛超敏反应,加剧 NP 。因此,抑制                               115-127.
                                             [11]
                                                              [ 6 ]  孙跃先,王九妹,崔新刚,等 . 穿心莲内酯调节 HMGB1/
          小胶质细胞活化以及促炎因子的释放为治疗NP提供了
                                                                   RAGE 信号通路对糖尿病周围神经病变大鼠坐骨神经
          新的思路。NP 可以触发 SP、PGE2等疼痛介质的释放,
                                                                   功能损伤的影响[J]. 中国药房,2024,35(5):572-577.
          其中SP是一种神经递质,能通过促进谷氨酸释放,从而
                                                                   SUN Y X,WANG J M,CUI X G,et al. Impacts of an‐
          参与疼痛传递;PGE2是一种重要的脂质介质,由环氧合
                                                                   drographolide  on  sciatic  nerve  function  damage  in  dia‐
          酶产生,可通过促进脊髓背角的突触传递来促进炎症性                                 betic  peripheral  neuropathy  rats  by  regulating  HMGB1/
                  [12]
          疼痛敏化 。本研究结果显示,与模型组比较,穿心莲                                 RAGE signaling pathway[J]. China Pharm,2024,35(5):
          内酯各剂量组大鼠的 MWT、TWL 均显著升高,炎症因                              572-577.
          子IL-6、TNF-α 和疼痛介质PGE2、SP 水平以及小胶质细                   [ 7 ]  FAN W,LIU C,CHEN D C,et al. Ozone alleviates MSU-
          胞活化标志物 Iba-1 mRNA 及蛋白表达量均显著降低。                           induced  acute  gout  pain  via  upregulating  AMPK/GAS6/
          这提示,穿心莲内酯可能通过抑制炎症反应来缓解NP。                                MerTK/SOCS3 signaling pathway[J]. J Transl Med,2023,
          另外,本研究设置了阿魏酸钠组作为阳性对照,结果显                                 21(1):890.
          示,高剂量穿心莲内酯缓解 NP 的作用与阿魏酸钠基本                          [ 8 ]  QIAN C,FAN Y X,ZONG L J,et al. Opening KATP chan‐
          相同。                                                      nels induces inflammatory tolerance and prevents chronic
                                                                   pain[J]. Brain Behav Immun,2023,107:76-86.
              已有研究发现,Gas6 可在体外抑制促炎细胞因子
                                                              [ 9 ]  KOGO Y,KOEBIS M,KOBAYASHI Y,et al. Analgesic
         (TNF、IL-6 和 IL-1β)的释放,激活 Gas6/Axl 信号轴,抑
                                                                   effect  of  safinamide  mesylate  in  a  rat  model  of  neuro‐
          制机械性异常性疼痛,并诱导炎症耐受以缓解神经炎症
                                                                   pathic pain[J]. Behav Brain Res,2023,452:114555.
                    [8]
          和术后疼痛 。Gas6 通过调节 Axl/Rac1 信号传导,促进
                                                              [10]  王士珍,张晓蕾,丁苏彭,等. 小檗碱对神经病理性疼痛
          小胶质细胞胞吐作用和防止炎症反应来减轻神经损                                   大鼠疼痛行为及IRAK1/TRAF6信号通路介导的神经炎
            [13]
          伤 。Gas6、Axl 信号转导缺失会导致神经损伤小鼠促                             症的影响[J]. 中国病理生理杂志,2022,38(9):1561-
          炎因子水平显著升高,并加重神经损伤小鼠运动缺                                   1568.
            [14]
          陷 。本研究结果显示,与模型组比较,穿心莲内酯各                                 WANG S Z,ZHANG X L,DING S P,et al. Effects of ber‐
          剂量组和阿魏酸钠组大鼠脊髓组织中 Gas6、Axl mRNA                           berine on pain behavior and neuroinflammation mediated
          及蛋白表达量均显著升高。这提示,穿心莲内酯可能通                                 by IRAK1/TRAF6 signaling pathway in neuropathic pain
          过激活Gas6/Axl信号轴来抑制炎症反应,从而发挥缓解                             rats[J]. Chin J Pathophysiol,2022,38(9):1561-1568.
          NP的作用。                                              [11]  CRISTIANO  C,GIORGIO  C,COCCHIARO  P,et  al.
              综上所述,穿心莲内酯可能通过激活Gas6/Axl信号                           Inhibition of C5aR1 as a promising approach to treat taxane-
                                                                   induced neuropathy[J]. Cytokine,2023,171:156370.
          轴来抑制炎症反应,从而发挥缓解 NP 的作用。后续本
                                                              [12]  FENG  L  M,CHEN Y Y,XU  D  Q,et  al. An  integrated
          研究将进一步使用 Gas6/Axl 信号轴相关激活剂或抑制
                                                                   strategy for discovering effective components of Shaoyao
          剂深入验证穿心莲内酯的相关作用机制。
                                                                   Gancao  decoction  for  treating  neuropathic  pain  by  the
          参考文献                                                     combination of partial least-squares regression and multi-
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               immune mechanisms in neuropathic pain[J]. Nat Rev Neu‐  260:113050.
               rol,2023,19(4):199-220.                        [13]  TANG J J,JIN Y C,JIA F,et al. Gas6 promotes microglia
          [ 2 ]  KIM K H,SEO H J,ABDI S,et al. All about pain pharma‐  efferocytosis and suppresses inflammation through activa-
               cology:what  pain  physicians  should  know[J].  Korean  J   ting Axl/Rac1 signaling in subarachnoid hemorrhage mice
               Pain,2020,33(2):108-120.                            [J]. Transl Stroke Res,2023,14(6):955-969.
          [ 3 ]  ZENG B,WEI A L,ZHOU Q,et al. Andrographolide:a   [14]  RAY A  K,DUBOIS  J  C,GRUBER  R  C,et  al.  Loss  of
               review  of  its  pharmacology,pharmacokinetics,toxicity   Gas6 and Axl signaling results in extensive axonal damage,
               and clinical trials and pharmaceutical researches[J]. Phyto‐  motor deficits,prolonged neuroinflammation,and less
               ther Res,2022,36(1):336-364.                        remyelination  following  cuprizone  exposure[J].  Glia,
          [ 4 ]  LIN Y  L,LIAO  J  W,WANG  S,et  al. Andrographolide     2017,65(12):2051-2069.
               relieves post-operative wound pain but affects local angio‐  (收稿日期:2024-04-03  修回日期:2024-06-12)
               genesis[J]. Pharmaceuticals,2022,15(12):1586.                                      (编辑:邹丽娟)



          · 2492 ·    China Pharmacy  2024 Vol. 35  No. 20                            中国药房  2024年第35卷第20期
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