혈관이식술 후 내막과다증식에 대한 Epigallocatechin-3-Gallate의 효과

The Effect of Epigallocatechin-3-Gallate on Intimal Hyperplasia after Vascular Grafting

  • 박한기 (연세대학교 의과대학 흉부외과학교실) ;
  • 송석원 (연세대학교 의과대학 흉부외과학교실) ;
  • 이미희 (연세대학교 의과대학 의학공학교실) ;
  • 박종철 (연세대학교 의과대학 의학공학교실) ;
  • 주현철 (연세대학교 의과대학 흉부외과학교실) ;
  • 장병철 (연세대학교 의과대학 흉부외과학교실) ;
  • 박영환 (연세대학교 의과대학 흉부외과학교실)
  • Park, Han-Ki (Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine) ;
  • Song, Suk-Won (Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine) ;
  • Lee, Mi-Hee (Department of Medical Engineering, Yonsei University College of Medicine) ;
  • Park, Jong-Chul (Department of Medical Engineering, Yonsei University College of Medicine) ;
  • Joo, Hyun-Chul (Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine) ;
  • Chang, Byung-Chul (Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine) ;
  • Park, Young-Hwan (Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine)
  • 발행 : 2007.04.05

초록

배경: 혈관내막과다증식은 혈관평활근세포가 내막에서 과다증식하여 나타나며, epigallocatechin-3-gallate(EGCG)는 혈관평활근세포의 증식을 억제하는 효과가 있는 것으로 알려져 있다. 따라서 EGCG는 혈관내막과다증식을 억제할 수 있을 것으로 생각된다. 대상 및 방법: 다른 농도의 EGCG를 포함한 배양 배지에서 인간제대정 맥내피세포(HUVEC)와 쥐대동맥평활근세포(RASMC)를 배양하고, 세포증식과 이동속도를 측정하였다. 20마리의 개의 양측 경동맥에 자가경정맥을 이식하였으며, 실험군(n=10)에 대해서는 정맥도관을 이식 전 30분간 EGCG용액에 보관하였으며, 이식 후 300mM의 EGCG를 혈관주위에 도포하였다. 6주 후에 경정맥이식편의 내막과 중간막의 두께를 측정하였다. 결과: 내피세포와 혈관평활근세포의 증식은 EGCG에 의해 억제되었다. 혈관평활근세포의 이동성은 EGCG에 의해 억제되었으나, 내피세포의 이동성은 영향을 받지 않았다. 동물실험 결과 대조군에 비해 EGCG군에서 내막의 두께가 얇았으며(p<0.05), 중간막의 두께는 두 군간에 차이가 얼었고, 내막/중간막의 두께비는 EGCG군에서 낮게 관찰되었다(p<0.05). 결론: EGCG는 혈관수술 후 혈관내막과다증식을 억제하는 효과가 있으며, 이는 혈관평활근세포의 증식 및 이동을 억제하여 효과를 나타낸다고 생각된다. 따라서 EGCG는 혈관내막과다증식을 예방하는 치료에 효과적으로 사용될 수 있을 것으로 생각된다.

Background: Intimal hyperpiasia is characterized by a proliferation of vascular smooth muscle cells in the intimal layer Epigallocatechin-3-gallate (EGCG) is known to suppress smooth muscle cell proliferation. We propose that EGCG may have a protective effect against the development of intimal hyperplasia through the suppression of smooth muscle cell proliferation. Material and Method: Human umbilical vein endothelial cells (HUVEC) and rat aortic smooth muscle cells (RASMC) were cultured with different concentrations of EGCG, and proliferation and migration speed were measured. In 20 dogs, the autologous jugular veins were interposed into the carotid arteries. For the study group (n=10), the graft was stored for 30 minutes in EGCG solution and 300mM EGCG was applied to the perivascular space after grafting. After 6 weeks, the intimal and medial thickness was measured. Result: The proliferation of RASMC and HUVEC was suppressed with EGCG. The migration of RASMC was suppressed with EGCG, but that of HUVEC was not affected. In the in vivo study, the intimal thickness was thinner in EGCG group than in the control group (p<0.05), but the medial thickness did not show any difference. The intimal/medial thickness ratio was lower in the EGCG group (p<0.05). Conclusion: EGCG suppresses intimal hyperplasia after vascular grafting, and this may be mediated by prevention of migration and proliferation of vascular smooth muscle cells. The use of EGCG may offer new therapeutic modality to prevent intimal hyperplasia.

키워드

참고문헌

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