ホモプランタギニンは,YES関連タンパク質1を調節することにより,高グルコース誘発の血管内皮壁機能障害を緩和します
Xulu Li1, Jingwen Wang1, Lei Wang1
1School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 639 Longmian Avenue, Nanjing 211198, China.
まとめ
ホモプランタギニン (HPG) は,YAP1/SIRT1/HMGB1経路を調節することにより,高血糖の損傷から血管内皮膜 (VE) 壁を保護します. この天然化合物は,糖尿病のマクロ血管合併症の治療に有望であることが示されています.
科学分野:
- エンドクリノロジー エンドクリノロジー
- 分子生物学は分子生物学である.
- 薬理学 薬理学とは
背景:
- 血管内皮膜 (VE) バリア機能障害は,糖尿病のマクロ血管合併症の重要な要因です.
- Salvia plebeia R.Br.から派生したホモプランタギニン (HPG) は,内皮を保護する性質を示しているが,糖尿病状態におけるメカニズムは不明である.
研究 の 目的:
- 高グルコース (HG) 治療を受けたヒト静脈内皮細胞 (HUVECs) と1型糖尿病 (T1D) のマウスにおけるVEバリア機能に対するHPGの保護効果を調査する.
- HPGの作用の基礎となる分子メカニズムを解明する.
主な方法:
- 実験室内試験 (ウェスタン・ブロッティング,RT-qPCR,免疫光,トランスエンドセリア電気抵抗,トランスウェル透過性) で,HPGがHUVECに与える影響を評価した.
- 治療効果を評価するために,T1DマウスにHPGまたはEX-527 (SIRT1阻害剤) を投与したイン・ビボ試験が実施されました.
主要な成果:
- HPGはVE-カデリン,ZO-1,オクラウディン,クラウディン-1を調節し,HG-HUVECにおける透過性とHMGB1転位を低下させた.
- HPGはYAP1のリン酸化を抑制し,核転位を促進し,YAP1-SIRT1の相互作用を強化し,直接的な相互作用が確認されました.
- HPGは,T1Dマウスのグルコース/脂質代謝を改善し,酸化ストレス/炎症を軽減し,内皮壁機能を強化し,大動脈損傷を弱めたが,EX-527によって効果は逆転した.
結論:
- HPGは,YAP1/SIRT1/HMGB1経路経由による高グルコース誘発のVEバリア機能不全を防ぎます. YAP1/SIRT1/HMGB1経路経由による高グルコース誘発のVEバリア機能不全を防ぎます.
- HPGは,糖尿病のマクロ血管合併症の管理のための潜在的な治療候補である.
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