カーノソルはp62-KEAP1-NRF2信号経路によるAng II誘発性腎損傷を弱める
Shijie Fan1, Ying Zhao1, Qingqing Zhao1
1Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Toxicology and applied pharmacology
|August 23, 2025
まとめ
Carnosol (Car) は腎臓損傷と酸化ストレスを軽減することによって,高血圧性腎臓疾患 (HRD) を効果的に治療します. これはp62-KEAP1-NRF2経路を活性化することで作用し,関連する腎臓損傷に対する新たな治療法となる可能性があります.
科学分野:
- 腎臓科
- 酸化ストレスに関する研究
- 薬理学について
背景:
- 高血圧は腎疾患,特に高血圧性腎疾患 (HRD) の主要な原因です.
- レドックスホメオスタシスは高血圧に関連した腎臓疾患において重要です.
- カーノゾール (Car) は既知の抗酸化物質ですが,HRDにおけるその役割は未研究です.
研究 の 目的:
- 高血圧性腎臓疾患に対する Carnosol の治療効果を調査する.
- HRDにおけるCarnosolの作用の基礎となる薬理学的メカニズムを解明する.
主な方法:
- 腎臓損傷と酸化ストレスを誘発するためにアンジオテンシンII (Ang II) を用いたin vitroおよびin vivo実験.
- Carnosol (40 mg/kg) を投与して,その効果を評価する.
- mTORとmTORC1を含むp62-KEAP1-NRF2経路の分析
主要な成果:
- カーノソルは,Ang IIによる腎臓損傷と酸化ストレスを有意に改善しました.
- mTORの相互作用によってp62のリン酸化が促進され,KEAP1の分解とNRF2の活性化につながった.
- NRF2のアップレギュレーションにより,抗酸化遺伝子の発現が増加しました.
- mTORC1の抑制は,p62と抗酸化機能に対するCarnosolの効果を無効にしました.
結論:
- カーノソルはp62- KEAP1- NRF2経路を活性化し,Ang II誘発のHRDにおける腎臓損傷と酸化ストレスを軽減します.
- Carnosolは,Ang IIによる腎臓損傷の予防と治療のための治療薬としての可能性を証明しています.
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