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TLR4/MyD88/NF-κB経路に基づくLPS誘発ゼブラフィッシュ炎症モデルへのヒペリンの抗炎症メカニズムの試験

  • role： First author第一作者
  • Affiliation：

    Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases， Hunan University of Chinese Medicine， Changsha 410208， China

  • Email：1985257811@qq.com
  • Introduction：兰晴，从事中西医结合神经退行性疾病防治研究，E-mail：1985257811@qq.com
LAN Qing,  
  • Affiliation：

    Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases， Hunan University of Chinese Medicine， Changsha 410208， China

WANG Anna,  
  • Affiliation：

    Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases， Hunan University of Chinese Medicine， Changsha 410208， China

ZHOU Feifei,  
  • Affiliation：

    Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases， Hunan University of Chinese Medicine， Changsha 410208， China

LIU Keqian,  
  • Affiliation：

    Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases， Hunan University of Chinese Medicine， Changsha 410208， China

LI Zhao,  
  • Affiliation：

    Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases， Hunan University of Chinese Medicine， Changsha 410208， China

YU Wenjing,  
  • Affiliation：

    Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases， Hunan University of Chinese Medicine， Changsha 410208， China

TANG Shuyao,  
  • Affiliation：

    Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases， Hunan University of Chinese Medicine， Changsha 410208， China

LI Ping,  
  • Affiliation：

    Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases， Hunan University of Chinese Medicine， Changsha 410208， China

CHENG Shaowu,  
  • role： Corresponding author通信作者
  • Affiliation：

    Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases， Hunan University of Chinese Medicine， Changsha 410208， China

  • Email：sisideng@hnucm.edu.cn
  • Introduction：邓思思，博士，讲师，从事中西医结合神经退行性疾病防治研究，E-mail：sisideng@hnucm.edu.cn；
DENG Sisi*,  
  • role： Corresponding author通信作者
  • Affiliation：

    Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases， Hunan University of Chinese Medicine， Changsha 410208， China

  • Email：songzhenyan2013@hnucm.edu.cn
  • Introduction：宋祯彦，博士，副教授，从事中西医结合神经退行性疾病防治研究，E-mail：songzhenyan2013@hnucm.edu.cn
SONG Zhenyan*

サマリー

この研究の目的は、フラボノイド化合物ヒペリン（Hyp）が脂多糖（LPS）誘発ゼブラフィッシュ炎症モデルに対する介入作用およびその潜在的なメカニズムを探ることでした。ゼブラフィッシュの幼魚には0.5 g·L-1 LPSをマイクロインジェクション、または1 g·L-1 LPSに浸し法を用いて炎症モデルを構築し、異なる濃度のHyp（25、50、100 mg·L-1）を連続4日間浸漬処置をしました。死亡率、奇形率、体長、黄卵巣袋面積率を分析して炎症表現型を評価し、行動学的検査で幼魚の炎症ストレス反応を評価しました。顕微鏡を用いてマクロファージの移動を観察し、リアルタイムPCRによって炎症関連遺伝子の白血球介素-1β（IL-1β）、白血球介素-6（IL-6）、マクロファージ趨化因子C-Cケミカルユニオン2（CCL2）、趨化因子C-X3-C-ケミカルユニオン受容部1（CX3CR1）、趨化因子C-C-ケミカルユニオン受容部2（CCR2）およびToll様受容部4（TLR4）/骨髄分化因子88（MyD88）/核転写因子-κB（NF-κB）シグナル経路の相関遺伝子mRNA発現を測定しました。純水注射グループと比較して、モデルグループのゼブラフィッシュ幼魚の死亡率、奇形率、黄卵巣袋面積が有意に上昇（P0.01）、体長が有意に低下（P0.01）、泳ぎ総距離、高速泳ぎ時間が有意に増加（P0.01）、TLR4、MyD88、NF-κB、IL-1β、IL-6、CCL2、CX3CR1、CCR2のmRNA発現が有意に上昇しました（P0.01）。モデルグループと比較して、Hypの低、中、高用量グループおよびアスピリングループは死亡率、奇形率が有意に低下（P0.05、P0.01）、体長が有意に増加（P0.05、P0.01）、黄卵巣袋面積率が有意に低下（P0.01）、高速泳ぎ時間が有意に減少しました（P0.01）、TLR4、MyD88、NF-κB、IL-1β、IL-6、CCL2、CX3CR1、CCR2のmRNA発現が有意に低下しました（P0.05、P0.01）。結論：HypはTLR4/MyD88/NF-κB経路を調節し、ゼブラフィッシュの炎症表現型を改善し、ストレスを軽減することで抗炎症作用を発揮する。

キーワード

ゼブラフィッシュ;炎症;ヒペリン;Toll様受容部4;骨髄分化因子88;核転写因子-κB

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