阻害性睡眠無呼吸症候群における断続的な低酸素による炎症経路の選択的活性化
Silke Ryan1, Cormac T Taylor, Walter T McNicholas
1Sleep Research Laboratory, St Vincent's University Hospital, Dublin, Ireland.
Circulation
|October 26, 2005
まとめ
阻害性睡眠無呼吸症候群 (OSAS) は,間欠性低酸素/低酸素化 (IHR) のとき,適応性のあるものではなく,炎症経路を活性化します. この選択的炎症は,OSAS患者の心血管疾患を誘発する可能性があります.
科学分野:
- 心血管疾患に関する研究
- スリープ・メディシン (睡眠医学)
- 分子生物学は分子生物学である.
背景:
- 阻害性睡眠無呼吸症候群 (OSAS) は,中断性低酸素/低酸素化 (IHR) と関連した心血管疾患の重要なリスク因子です.
- OSASと心血管合併症を結びつける正確な分子メカニズムについては,さらなる解明が必要である.
研究 の 目的:
- OSASと心血管疾患との関連を裏付ける分子メカニズムを調査する.
- IHRに対する反応として炎症経路と適応経路の活性化を,トランスレーションモデルで検証する.
主な方法:
- IHRに曝されたインビトロHeLa細胞モデルを利用し,レポーター構造とDNA結合アッセイを用いてNF-kappaBとHIF-1を研究した.
- 男性OSAS患者とマッチングされたコントロールのプロスペクティブ研究を実施し,循環腫瘍ネクロシス因子-アルファ,エリトロポエチン,中性粒子のレベル,および血圧を測定しました.
- 6週間の継続的な陽性気道圧 (CPAP) 治療後のOSAS患者の評価変化.
主要な成果:
- In vitro IHRでは,炎症性転写因子NF-kappaBを選択的に活性化させ,適応性調節因子HIF-1は非活性化させました.
- OSASの患者は,対照群と比較して,炎症性サイトカイン腫瘍ネクロシス因子アルファと中性粒子の数の循環レベルが高かった.
- CPAP療法は,OSAS患者における腫瘍死滅因子-αレベルを正常化させ,エリトロポエチンレベルと血球値は変化しなかった.
結論:
- この研究は,IHRおよびOSASの間に適応経路よりも炎症経路の選択的活性化を示しています.
- 炎症を助長するこの不均衡は,OSASにおける心血管疾患に貢献する重要な分子メカニズムとして提案されています.
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