PDF(Pubmed)
Abstract：
BACKGROUND: Gastrodin (GAS), a main bioactive component of the herbal plant, Gastrodia elata Blume, has shown to have beneficial effects on neuroinflammatory diseases such as Alzheimer\'s disease in animal studies and migraine in clinical studies. Inflammasome is a multimeric protein complex having a core of pattern recognition receptor and has been implicated in the development of neuroinflammatory diseases. Gastrodin has shown to modulate the activation of nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. This study investigated the effects of GAS on the intensity of mechanical allodynia and associated changes in NLRP3 inflammasome expression at the spinal level using L5/6 spinal nerve ligation model (SNL) in rats.
METHODS: Intrathecal (IT) catheter implantation and SNL were used for drug administration and pain model in male Sprague-Dawley rats. The effect of gastrodin or MCC950 (NLRP3 inflammasome inhibitor) on mechanical allodynia was measured by von Frey test. Changes in NLRP3 inflammasome components and interleukin-1β (IL-1β) and cellular expression were examined in the spinal cord and dorsal root ganglion.
RESULTS: The expression of NLRP3 inflammasome components was found mostly in the neurons in the spinal cord and dorsal root ganglion. The protein and mRNA levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and IL-1β were upregulated in SNL animals compared to Sham animals. IT administration of GAS significantly attenuated the expression of NLRP3 inflammasome and the intensity of SNL-induced mechanical allodynia. NLRP3 inflammasome inhibitor, MCC950, also attenuated the intensity of allodynia, but the effect is less strong and shorter than that of GAS.
CONCLUSIONS: Expression of NLRP3 inflammasome and IL-1β is greatly increased and mostly found in the neurons at the spinal level in SNL model, and IT gastrodin exerts a significant anti-allodynic effect in SNL model partly through suppressing the expression of NLRP3 inflammasome.
METHODS: Intrathecal (IT) catheter implantation and SNL were used for drug administration and pain model in male Sprague-Dawley rats. The effect of gastrodin or MCC950 (NLRP3 inflammasome inhibitor) on mechanical allodynia was measured by von Frey test. Changes in NLRP3 inflammasome components and interleukin-1β (IL-1β) and cellular expression were examined in the spinal cord and dorsal root ganglion.
RESULTS: The expression of NLRP3 inflammasome components was found mostly in the neurons in the spinal cord and dorsal root ganglion. The protein and mRNA levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and IL-1β were upregulated in SNL animals compared to Sham animals. IT administration of GAS significantly attenuated the expression of NLRP3 inflammasome and the intensity of SNL-induced mechanical allodynia. NLRP3 inflammasome inhibitor, MCC950, also attenuated the intensity of allodynia, but the effect is less strong and shorter than that of GAS.
CONCLUSIONS: Expression of NLRP3 inflammasome and IL-1β is greatly increased and mostly found in the neurons at the spinal level in SNL model, and IT gastrodin exerts a significant anti-allodynic effect in SNL model partly through suppressing the expression of NLRP3 inflammasome.
摘要：
背景：天麻素（GAS），草药植物的主要生物活性成分，天麻,已证明对神经炎症性疾病如阿尔茨海默病的动物研究和偏头痛的临床研究具有有益的作用。炎症小体是一种具有模式识别受体核心的多聚体蛋白复合物，与神经炎性疾病的发展有关。天麻素已显示出调节核苷酸结合寡聚化结构域（NOD）样受体蛋白3（NLRP3）炎性体的激活。本研究使用大鼠L5/6脊神经结扎模型（SNL）研究了GAS对机械异常性疼痛强度的影响以及在脊髓水平上NLRP3炎性体表达的相关变化。
方法：鞘内（IT）导管植入和SNL用于雄性SD大鼠的给药和疼痛模型。天麻素或MCC950(NLRP3炎性体抑制剂)对机械性异常性疼痛的作用通过vonFrey试验来测量。在脊髓和背根神经节中检查了NLRP3炎性体成分和白介素1β（IL-1β）的变化以及细胞表达。
结果：NLRP3炎性体成分主要在脊髓和背根神经节的神经元中表达。NLRP3，含有caspase募集结构域（ASC）的凋亡相关斑点样蛋白的蛋白质和mRNA水平，与假动物相比,在SNL动物中caspase-1和IL-1β上调。GAS的IT给药显著减弱NLRP3炎性体的表达和SNL诱导的机械性异常性疼痛的强度。NLRP3炎性体抑制剂，MCC950也减弱了异常疼痛的强度，但效果不如GAS强和短。
结论：在SNL模型中，NLRP3炎性体和IL-1β的表达大大增加，并且主要在脊髓水平的神经元中发现，在SNL模型中，天麻素部分通过抑制NLRP3炎性体的表达发挥了显着的抗异常作用。
方法：鞘内（IT）导管植入和SNL用于雄性SD大鼠的给药和疼痛模型。天麻素或MCC950(NLRP3炎性体抑制剂)对机械性异常性疼痛的作用通过vonFrey试验来测量。在脊髓和背根神经节中检查了NLRP3炎性体成分和白介素1β（IL-1β）的变化以及细胞表达。
结果：NLRP3炎性体成分主要在脊髓和背根神经节的神经元中表达。NLRP3，含有caspase募集结构域（ASC）的凋亡相关斑点样蛋白的蛋白质和mRNA水平，与假动物相比,在SNL动物中caspase-1和IL-1β上调。GAS的IT给药显著减弱NLRP3炎性体的表达和SNL诱导的机械性异常性疼痛的强度。NLRP3炎性体抑制剂，MCC950也减弱了异常疼痛的强度，但效果不如GAS强和短。
结论：在SNL模型中，NLRP3炎性体和IL-1β的表达大大增加，并且主要在脊髓水平的神经元中发现，在SNL模型中，天麻素部分通过抑制NLRP3炎性体的表达发挥了显着的抗异常作用。
