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급성 척수손상 고양이에서 21-aminosteroid U74389F 투여가 척수혈류와 체성감각 유발전위에 미치는 영향

Other Titles
 (The) effects of 21-aminosteroid U74389F on posttraumatic spinal cord blood flow and somatosensory evoked potential 
Issue Date
1992
Description
의학과/박사
Abstract
[한글] 현재까지 척수손상의 발생기전은 아직 명확히 밝혀져 있지 않으나 첫째 외상에 의한 물 리적 손상과 둘째 생화학적인 반응에 의한 척수허혈 현상에 기인한다고 한다. 특히 비가 역적인 척수손상은 허혈현상에 기인한다고 알려져 있으므로 비가역적 손상이 오기전에 손 상된 부위의 국소혈류를 증가시킴으로써 신경조직의 괴사를 예방할 수 있고 신경학적 증 상을 개선시킬 수 있는 것으로 생각되고 있다. 척수손상후 허혈현상의 기전규명 및 치료에 관한 활발한 연구가 진행되어 왔으나 아직 도 명확한 기전을 밝혀내지 못하고 있으며 임상적 치료법도 완전히 정립되지 않았다. 특 히 척수혈류를 선택적으로 증가시킬수 있는 약물은 매우 드물며 그나마 현재 시도되고 있 는 약물들도 미흡한 효능과 부작용으로 임상적 적용에 제한이 많았다. Lipid peroxidation이 척수허혈증의 발생에서 핵심적인 역활을 하며 직접적인 원인이 된다는 사실이 밝혀졌다. 최근에 개발된 강력한 lipid peroxidation 억제제인 21-aminost eroid U74006F가 손상된 척수 및 뇌의 국소혈류 감소를 예방하고 실험적 뇌지주막하 출혈 후 혈관연축을 감소시킨다고 보고되었다. 본 연구에서는 제 1흉추부에 척수손상을 가한 고양이에서 손상부위의 척수혈류를 측정 하였고 좌골신경을 전기자극하여 제 5경추부 및 제 1요추부에서 유발되는 체성감각 유발 전위를 기록하여 U74006F의 유사물질인 21-aminosteroid U74389F가 척수혈류 및 체성감각 유발전위에 미치는 영향을 관찰하여 다음과 같은 결론을 얻었다. 1. 척수손상후 U74389F를 3mg/kg 투여했을 때 척수혈류는 손상전 혈류보다 통계적으로 유의한 감소를 보였으며 척수손상후 4시간후 체성감각 유발전위의 회복율은 0%이었다. 2. 척수손상후 U74389F를 각각 10mg/kg, 20mg/kg투여했을 때와, 손상전 10mg/kg 투여했 을때 혈류는 모두 손상전 수준에 가깝게 유지되었으며 체성감각 유발전위의 회복율은 40 ∼60%이었다. 3. 척수손상후 4시간후 척수혈류는 naloxone을 투여했을 때보다 통계적으로 유의한 증 가가 있었는데 그 이유는 혈청내에서 U74389F의 반감기가 naloxone보다 2배 가량 길기 때 문으로 생각된다. 4. 척수손상후 U74389F를 각각 10mg/kg, 20mg/kg 투여했을 때의 척수혈류변화는 서로 통계적으로 유의한 차이가 없었으며 U74389F 10mg/kg를 각각 척수손상전, 후에 투여했을 때의 척수혈류는 서로 통계적으로 유의한 차이없이 유지되었다. 즉 U74389F의 유효용량은 10mg/kg이상이며 투여시기는 척수혈류에 영향을 미치지 않는 것으로 생각된다. 이상의 연구 결과로 보아 U74389F는 척수손상후 척수혈류의 감소를 예방할 수 있으며 그 효과는 naloxone보다 오랫동안 지속되는 것으로 생각된다. 또 U74389F는 신경세포의 기능회복에도 도움이 될 가능성이 있는 것으로 생각되는데 신경학적 증상의 호전여부와 더불어 향후 더욱 추구해야될 과제라고 생각된다. The effects of 21-aminosteroid U74389F on posttraumatic spinal cord blood flow and somatosensory evoked potential. Jin Yang Joo Department of Medical Science The Graduate School, Yousei University (Directed by Professor Young Soo Kim) The pathogenesis of spinal cord injury has not been fully understood yet. However, there is evidence that spinal cord injury is progressed by two separate mechanisms: the initial mechanical damage and secondary ischemia due to biochemical effect. Because ischemia contributes to the irreversible spinal cord lesion, it is believed that secondary degeneration can be prevented and functional recovery can be expected by increasing the local blood flow. The mechanism of posttraumatic spinal cord ischemia has been studied but the perfect treatment proctocol has not been developed yet. There are few pharmacological agents reported to enhance the spinal cord blood flow after injury. Furthermore, their clinical application has been defective due to unsatisfactory effect and side reaction. A growing body of biochemical, physiological, and pharmacological evidence has suggested that oxy-gen free radical-induced lipid peroxidation plays a key role in progressive posttraumatic spinal cord is-chemia. Recently, it has been shown that newly developed compound, U74006F, a non-glucocorticoid 21-aminosteroid, is extremely potent as an inhibitor of lipid peroxidation and effective preventor from the posttraumatic ischemia. In this investigation, the effects of 21-aminosteroid U74389F, analog of U74006F, on posttraumatic spinal cord blood flow and somatosensory evoked potential have been studied in cats. The results of this study are summarized as fellows: 1. U74389F, given 3 ㎎/㎏, after spinal cord injury, blood flow decreased significantly and somatosensory response returned to none of five cats. 2. U74389F, given 10 ㎎/㎏, 20 ㎎/㎏ respectively after or before the spinal cord injury, the blood flow did not decreased and maintained near the preiniury level. 3. At 4 hours after injury, this less decrease of blood flow was statistically significant compared to much more decrease in naloxone-treated cats. The reason was thought to be much longer half life of U74389F in serum. The recovery rate of somatosensory evoked potential ranged from 40 to 60%. 4. There was no statistical difference of blood flow change between the cats treated with 10 ㎎/㎏ and those treated with 20 ㎎/㎏ of U74389F. It was thought that the adequate dosage of U74389F to pre-vent posttraumatic spinal cord ischemia was more than 10㎎/㎏ and timing of administration did not affect the blood flow. From the above results, it is speculated that U74389F has beneficial effect on posttraumatic spinal cord ischemia and functional recovery. The effects last longer than those of naloxone.
[영문] The pathogenesis of spinal cord injury has not been fully understood yet. However, there is evidence that spinal cord injury is progressed by two separate mechanisms: the initial mechanical damage and secondary ischemia due to biochemical effect. Because ischemia contributes to the irreversible spinal cord lesion, it is believed that secondary degeneration can be prevented and functional recovery can be expected by increasing the local blood flow. The mechanism of posttraumatic spinal cord ischemia has been studied but the perfect treatment proctocol has not been developed yet. There are few pharmacological agents reported to enhance the spinal cord blood flow after injury. Furthermore, their clinical application has been defective due to unsatisfactory effect and side reaction. A growing body of biochemical, physiological, and pharmacological evidence has suggested that oxy-gen free radical-induced lipid peroxidation plays a key role in progressive posttraumatic spinal cord is-chemia. Recently, it has been shown that newly developed compound, U74006F, a non-glucocorticoid 21-aminosteroid, is extremely potent as an inhibitor of lipid peroxidation and effective preventor from the posttraumatic ischemia. In this investigation, the effects of 21-aminosteroid U74389F, analog of U74006F, on posttraumatic spinal cord blood flow and somatosensory evoked potential have been studied in cats. The results of this study are summarized as fellows: 1. U74389F, given 3 ㎎/㎏, after spinal cord injury, blood flow decreased significantly and somatosensory response returned to none of five cats. 2. U74389F, given 10 ㎎/㎏, 20 ㎎/㎏ respectively after or before the spinal cord injury, the blood flow did not decreased and maintained near the preiniury level. 3. At 4 hours after injury, this less decrease of blood flow was statistically significant compared to much more decrease in naloxone-treated cats. The reason was thought to be much longer half life of U74389F in serum. The recovery rate of somatosensory evoked potential ranged from 40 to 60%. 4. There was no statistical difference of blood flow change between the cats treated with 10 ㎎/㎏ and those treated with 20 ㎎/㎏ of U74389F. It was thought that the adequate dosage of U74389F to pre-vent posttraumatic spinal cord ischemia was more than 10㎎/㎏ and timing of administration did not affect the blood flow. From the above results, it is speculated that U74389F has beneficial effect on posttraumatic spinal cord ischemia and functional recovery. The effects last longer than those of naloxone.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/117092
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2. 학위논문 > 1. College of Medicine (의과대학) > 박사
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