활성 산소종에 의한 토끼 복부 대동맥의 혈관 내피세포 손상에 미치는 근이완제(Vecuronium, Rocuronium)의 항산화 효과
- Title
- 활성 산소종에 의한 토끼 복부 대동맥의 혈관 내피세포 손상에 미치는 근이완제(Vecuronium, Rocuronium)의 항산화 효과
- Other Titles
- Antioxidant Effects of Muscle Relaxants (Vecuronium, Rocuronium) on the Rabbit Abdominal Aortic Endothelial Damage Induced by Reactive Oxygen Species
- Author
- 정지선
- Alternative Author(s)
- Ji Seon Jeong
- Advisor(s)
- 서정국
- Issue Date
- 2013-08
- Publisher
- 한양대학교
- Degree
- Doctor
- Abstract
- 연구배경: 근이완제는 prostaglandin 합성을 증가시킴으로써 혈관 평활근을 이완시킨다. 그러나 근이완제가 활성 산소종(ROS)과 혈관 장력 사이의 관계에 미치는 영향에 대해서는 밝혀진 바가 없다. 본 연구에서는 ROS에 의하여 유발된 토끼 복부 대동맥 내피세포의 손상에 대한 근이완제의 영향을 알아보고자 하였다.
방법: 토끼 복부 대동맥 환상절편을 Krebs-Henseleit solution이 있는 실험조(organ bath) 내에서 근이완제인 vecuronium 및 rocuronium을 각각 10-4, 3 × 10-4, 10-3, 3 × 10-3 M의 농도로 15분간 전처치한 후에 전기 분해를 통해 ROS에 노출시켰다. 근이완제의 항산화 기전을 밝히기 위하여 Cu/Zn superoxide dismutase inhibitor인 diethyldithiocarbamate (DETCA, 0.8 mM)와 catalase inhibitor인 3-amino-1,2,4-triazole (3AT, 50 mM)를 각각 30분, 60분간 전처치를 하였다. 혈관 평활근의 이완 정도는 norepinephrine (10-6 M)으로 전수축 시킨 후에 acetylcholine에 의한 최대 이완에 대하여 전기분해 전과 후에 측정된 이완의 백분율로 하였다.
결과: 근이완제(vecuronium 및 rocuronium) 10-4, 3 × 10-4, 10-3, 3 × 10-3 M에 전처치로서 ROS에 의해 감소된 acetylcholine 10-6 M에 의한 혈관 평활근 이완을 용량 의존적으로 회복시켰다. 이러한 결과는 근이완제가 ROS에 대하여 항산화 효과가 있음을 암시한다. 항산화 억제제인 DETCA를 전처치한 vecuronium (p < 0.001), rocuronium (p < 0.001) 군에서는 항산화 효과가 억제되었지만, 3AT를 전처치한 군에서는 항산화 효과가 유지되었다.
결론: 근이완제(vecuronium 및 rocuronium)는 토끼의 복부 대동맥에서 활성 산소에 의한 내피세포 손상에 용량 의존적으로 보호작용이 있는 것을 확인 할 수 있었다. 이러한 항산화 효과는 superoxide anion scavenging과 관계가 있음을 알 수 있었다.
|Background: Muscle relaxants induces vascular smooth muscle relaxation due to increase in prostaglandin synthesis. But, for endothelial cell injuries by ROS, effects of muscle relaxants on vasomotor tone are unclear until now. We studied the influences of muscle relaxant (vecuronium, rocuronium) on the rabbit abdominal aortic endothelial damage induced by ROS
Methods: Isolated rabbit abdominal aorta ring segments were exposed to ROS generated by electrolysis of the organ bath medium (Krebs-Henseleit solution) after pretreatment with various concentrations (10-4, 3 × 10-4, 10-3, 3 × 10-3 M groups) of muscle relaxants (vecuronium, rocuronium). Effect of ROS scavenging of muscle relaxants was investigated using additional pretreatment of a Cu/Zn superoxide dismutase inhibitor diethyldithiocarbamate (DETCA, 0.8 mM) and a catalase inhibitor 3-amino-1,2,4-triazole (3AT, 50 mM). Degree of vascular smooth muscle relaxation measured by precontraction of the vessels with norepinephrine (10-6 M) followed by the cumulative addition of acetylcholine (range, 3 × 10-8 to 10-6 M) before and after ROS generation.
Results: Muscle relaxant (vecuronium, rocuronium) 10-4, 3 × 10-4, 10-3, 3 × 10-3 M groups recovered ACh 10-6 M induced endothelial dependent relaxation of aortic ring pretreated with ROS in a dose-dependent manner. Pretreatment with DETCA inhibited the antioxidant effect of vecuronium (p < 0.001) and rocuronium (p < 0.001), but pretreatment with 3AT did not have the same effect
Conclusions: Muscle relaxant (vecuronium, rocuronium) protect endothelium against free radical injury in a dose-dependent manner in isolated rabbit abdominal aortas. These results suggest that protective effect of them is caused by superoxide anion scavenging.; Background: Muscle relaxants induces vascular smooth muscle relaxation due to increase in prostaglandin synthesis. But, for endothelial cell injuries by ROS, effects of muscle relaxants on vasomotor tone are unclear until now. We studied the influences of muscle relaxant (vecuronium, rocuronium) on the rabbit abdominal aortic endothelial damage induced by ROS
Methods: Isolated rabbit abdominal aorta ring segments were exposed to ROS generated by electrolysis of the organ bath medium (Krebs-Henseleit solution) after pretreatment with various concentrations (10-4, 3 × 10-4, 10-3, 3 × 10-3 M groups) of muscle relaxants (vecuronium, rocuronium). Effect of ROS scavenging of muscle relaxants was investigated using additional pretreatment of a Cu/Zn superoxide dismutase inhibitor diethyldithiocarbamate (DETCA, 0.8 mM) and a catalase inhibitor 3-amino-1,2,4-triazole (3AT, 50 mM). Degree of vascular smooth muscle relaxation measured by precontraction of the vessels with norepinephrine (10-6 M) followed by the cumulative addition of acetylcholine (range, 3 × 10-8 to 10-6 M) before and after ROS generation.
Results: Muscle relaxant (vecuronium, rocuronium) 10-4, 3 × 10-4, 10-3, 3 × 10-3 M groups recovered ACh 10-6 M induced endothelial dependent relaxation of aortic ring pretreated with ROS in a dose-dependent manner. Pretreatment with DETCA inhibited the antioxidant effect of vecuronium (p < 0.001) and rocuronium (p < 0.001), but pretreatment with 3AT did not have the same effect
Conclusions: Muscle relaxant (vecuronium, rocuronium) protect endothelium against free radical injury in a dose-dependent manner in isolated rabbit abdominal aortas. These results suggest that protective effect of them is caused by superoxide anion scavenging.
- URI
- https://repository.hanyang.ac.kr/handle/20.500.11754/133101http://hanyang.dcollection.net/common/orgView/200000423051
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- GRADUATE SCHOOL[S](대학원) > MEDICINE(의학과) > Theses (Ph.D.)
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