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.