獐牙菜苦苷通过下调NLRP3抑制卫星胶质细胞炎性激活参与到蒙药秘诀红花-13味丸治疗偏头痛的功能与机理研究

Migraine is a common chronic neurovascular disease and the sixth crippling disease. Mongolian medicine Mijuehonghua-13 pills in the treatment of migraine has a significant clinical effect, but the mechanism of Mijuehonghua-13 pills is unknown.Pre-experimental studies have shown that Swertiamarin can inhibit inflammatory activation of satellite glial cells induced by CGRP and down regulate NLRP3 expression.It has no reports yet that NLRP3 paticipated in the inflammatory activation of SGC. We hypothesized that Swertiamarin inhibits inflammatory activation of satellite glial cells through downregulating NLRP3 Involved in Mongolian medicine Mijuehonghua-13 pills treatment of migraine. We will validate the hypothesis in SGC inflammatory activation model in vitro and Interfere with the expression of NLRP3 to verify the function of NLRP3 in SGC inflammatory activation; We will treat the inflammatory activation model SGC cells by Swertiamarin meanwhile intervene the expression of NLRP3 and detect the expression of inflammatory cytokines to validate that Swertiamarin inhibits inflammatory activation of SGC through downregulating NLRP3. In CGRP-Migraine rat model,we will treat the rats by Mijuehonghua-13 pills and detect the expression of NLRP3 and inflammatory cytokines such as IL-1β、IL-6、TNF-a to validate that it can inhibits inflammatory activation of SGC through downregulating NLRP3..The project will provide scientific basis to the clinical application of Mijuehonghua-13 pills in treatment of migraine.

偏头痛是常见的慢性神经血管性疾病，是第六位致残性疾病。蒙药秘诀红花-13味丸在临床治疗偏头痛中效果显著，但有效成分不清机理不明。预实验显示其成分獐牙菜苦苷可抑制CGRP诱导的卫星胶质细胞（SGC）炎性激活，并下调NLRP3。NLRP3是否参与到SGC炎性激活？目前未见报道。提出假设，獐牙菜苦苷通过下调NLRP3抑制SGC炎性激活参与到蒙药秘诀红花-13味丸治疗偏头痛当中。拟进行：体外SGC炎性激活模型，干预NLRP3的表达，验证NLRP3在SGC炎性活化中的功能；SGC激活模型中加入獐牙菜苦苷并进行NLRP3基因干预，检测炎性指标验证獐牙菜苦苷可通过NLRP3抑制SGC炎性激活；CGRP偏头痛大鼠模型给予秘诀红花-13味丸，检测NLRP3及IL-1β、IL-6、TNF-a，验证其可下调NLRP3，抑制SGC炎性活化。.本项目的开展，为蒙药秘诀红花-13味丸治疗偏头痛的临床使用提供科学依据。

偏头痛是常见的慢性神经血管性疾病，是第六位致残性疾病。蒙药秘诀红花-13味丸在临床治疗偏头痛中疗效显著，但有效成分不清机理不明。这在一定程度上阻碍了该药在其他地区的临床推广使用。本研究通过开展以下研究，从分子水平初步验证了该蒙药的临床疗效。主要研究内容为：体外LPS-BV2炎性激活模型，干预NLRP3的表达，验证NLRP3在LPS炎性活化中的功能；LPS激活模型中加入蒙药秘诀红花-13味丸的有效单体成分獐芽菜苦苷进行NLRP3基因干预，检测炎性指标验证獐芽菜苦苷可通过NLRP3抑制LPS-BV2炎性激活；偏头痛大鼠模型给予秘诀红花-13味丸，检测NLRP3及IL-1β、IL-6、IL-18、TNF-a，验证蒙药秘诀红花-13味丸可下调NLRP3，抑制BV2炎性活化。实验结果表明獐芽菜苦苷可抑制炎症，降低IL-1β、IL-6、IL-18、TNF-a的水平。本研究的开展，为蒙药秘诀红花-13味丸治疗偏头痛的临床推广使用提供科学依据。