과잉 철로 유도된 산화적 스트레스가 혈소판 활성화에 미치는 작용

국문 초록 (Abstract)

과잉 철은 폐경기 여성 및 핀란드 남성에서의 심혈관계질환 증가와 예방통계학적으로 밀접한 관련이 있다고 보고되고 있다. 허혈성 심장질환, 뇌ㆍ심혈관계 질환, 암 및 노화의 원인으로 산화적 스트레스가 자유기 반응을 자극하고 지질과산화 반응 등을 연쇄적으로 촉진시키는데 철이 위험 인자로 인식되고 있다. 그러나 뇌심혈관계 질환 유발의 중요인자인 혈소판 활성화와 관련하여 철로 인한 산화적 스트레스와 항산화작용의 연구는 부족하다고 한다. 산화적 스트레스에서 철 및 과산화수소의 자유기 형성과 관련하여 토끼 혈액에서 분리한 세정 혈소판을 사용하여 연구하였다. 산화적 스트레스를 통해 혈소판 응집을 유도하고 이에 미치는 영향을 연구한 결과에서 H₂O₂ 단독 투여시 혈소판 응집작용은 나타나지 않았다. FeSO₄ 단독 투여시 농도 의존적으로 혈소판 응집작용이 증가하여 나타내지만, H₂O₂ 존재 하에 FeSO₄ 투여시 농도 의존적으로 혈소판 응집작용이 증가되어 나타났다. 혈소판 응집을 유도하는 collagen 최적의 농도(2 ㎍/mL)보다 낮은 1/10 농도(0.2 ㎍/mL)에서 H₂O₂ 및 FeSO₄의 영향은 농도 의존적으로 혈소판 응집작용이 증가되었다. 철단독 투여시보다 과산화수소와 함께 투여시 농도 의존적으로 혈소판 활성화가 증대되었고 이러한 혈소판 활성화는 NAD/NADP, catalase, glutathione, mannitol, tiron 등에 의해 농도 의존적으로 억제되었고, NADH/NADPH, SOD, aspirin 등에 의해서는 영향이 없었다. 그러므로, 이러한 NAD(H)/NADP(H) cofactor는 혈소판 응집작용을 일으키는 radical을 직접 억제하기보다 radical 생성에 관련하는 것으로 사료된다. 이상의 결과에서 과잉철은 혈소판 활성화에 직접적으로 관여하고 H₂O₂ 존재하에 2가 철을 촉매로 하여 Fenton 반응으로 생성된 OHㆍ자유기가 혈소판 활성화에 중요한 역할을 한다. 그러나 혈소판에서 자유기가 arachidonic acid 대사의 활성화와 인산화 단백질로 인한 세포내 정보전달에 관한 연구가 더 이루어져야 한다고 사료된다.

다국어 초록 (Multilingual Abstract)

Although iron is essential for many physiological processes, excess iron can lead to tissue damage by promoting the generation of reactive oxygen species (ROS). There is increasing evidence that ROS might play an important role in the pathogenesis of cardiovascular disease. However, the effects of iron excess on platelet function and the thrombotic response to vascular injury are not well understood. We examined the effects of iron excess?induced oxidative stress and the antioxidants on platelet aggregation. Oxidative stress was accessed by either free iron (Fe?²) or hydrogen peroxide (H₂O₂), as well as their combination on washed rabbit platelets (WPs) in vitro. When WPs were stimulated with either Fe?² alone or a subthreshold concentration of collagen, which gave an aggregatory curve with a little effect, and a dose dependent increase in platelet aggregation was observed by increasing concentrations of Fe?² with H₂O₂. This aggregation was associated with the iron-catalyzed formation of hydroxyl radicals from H₂O₂, and were inhibited by NAD/NADP (proton acceptor), catalase (H₂O₂ scavenger), tiron (iron chelator), mannitol (hydroxyl radical scavenger), and indomethacin (cyclooxygenase inhibitor), but not by NADH/NADPH (proton donor), superoxide mutase, and aspirin. However, NADH/NADPH, an essential cofactor for the antioxidant capacity by the supply of reducing potentials, showed the effect of an enhanced radical formation, suggesting a role for NADH/NADPH-dependent oxidase. These results suggest that iron (Fe?²) can directly interact with washed rabbit platelets and this aggregation be mediated by OH? formation as in the Fenton reaction, inhibited by radical scavengers.

목차 (Table of Contents)

• Abstract
• 서론
• 재료 및 방법
• 결과 및 고찰
• 요약
• 문헌

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