Effects of Inducible NOS Inhibition on Motor Function Recovery After Sciatic Nerve Ischemia and Reperfusion in Rats

국문 초록 (Abstract)

목적: 말초 신경의 허혈-재관류 손상에서 산화질소 역할에 대한 연구가 활발히 진행되고 있다. 그러나 세 종류의 산화질소 생성효소 중 유발 산화질소 생성효소의 말초 신경 손상에서의 작용은 여러 가지 다양한 결과들이 보고되고 있다. 본 논문은 백서 좌골 신경의 허혈-재관류 손상에서 유발 산화질소 생성효소 억제가 운동 기능 회복에 미치는 영향에 관하여 알아보고자 하였다.
대상 및 방법: 170마리의 백서를 유발 산화질소 생성효소 특이 억제재인 1400W를 투여한 실험군과 증류수를 투여한 대조군으로 나누었다. 각 군 백서의 좌골 신경에 2시간 동안 특별히 고안된 기계로 압박을 가해 허혈을 유발한 후 42일까지의 재관류 기간 동안 운동 기능 회복, 허혈 신경의 조직학적 검사, 유발 산화질소 생성효소의 mRNA와 단백질 발현 변화를 관찰하였다.
결과: 좌골 신경 운동 기능 지수로 측정한 운동 기능은 재관류 후 11일부터 실험군에서 의미 있게 빠르게 회복되었다. 특히 재관류 18일에 두 군 사이에 가장 큰 차이를 보였으며(실험군; -46.8, 대조군; -29.4) 재관류 28일 후에는 차이가 없었다. 전체 회복 속도는 실험군이 약 일주일 정도 빠른 회복을 나타내었다. 허혈 신경의 조직학적 소견은 실험군에서 대조군보다 빠른 신경 섬유 회복 및 축삭 퇴행 지연이 관찰되었다. 유발 산화질소 생성효소의 mRNA와 단백질 발현은 재관류 첫 3일 동안 정상 발현량보다 의미있게 증가하였다가 감소하였다. 1400W는 증가된 유발 산화질소 생생효소 mRNA와 단백질 발현을 재관류 7일까지 통계학적으로 의미 있게 감소시켰다.
결론: 말초 신경 허혈 후 유발 산화질소 생성효소의 재관류 초기 억제가 유발 산화질소 생성효소 mRNA와 단백질 발현을 감소시켜 재관류 전 기간 동안 신경을 빠르게 회복시켰다. 유발 산화질소 생성효소의 억제가 말초 신경 허혈-재관류 손상 예방 및 치료의 한 방법이 될 수 있을 것으로 사료된다.

다국어 초록 (Multilingual Abstract)

Purpose: Introduction: Nitric oxide (NO) is known to play an important role in ischemia and reperfusion (I/R) injuries in the peripheral nerve. However, among various NO synthases (NOS), the effects of inducible NOS (iNOS) on peripheral nerve I/R injuries are still under debate. This study presents the influence of iNOS on the regeneration of crushed peripheral nerve in rats.
Materials and Methods: One hundred and seventy female Sprague-Dawley rats (body weights 175-200 g) were randomly divided into two groups to receive an injection of 1400W (iNOS specific inhibitor, 3 ㎎/㎏) or the same volume of purified water. One sciatic nerve of each rat (10 ㎜ in length) was subjected to a 100-g crush load for 2 hours to induce ischemia. Motor functional recovery by walking track test and histology of the crushed nerve in the two groups were evaluated at different reperfusion time (3 hours, and 1, 3, 7, 11, 14, 21, 28, 35, and 42 days). mRNA and protein levels for iNOS in the nerve were measured.
Results: Sciatic functional index (SFI) for motor functional recovery in the 1400W treated group improved at a significantly faster rate than that in the control group from day 11 after the ischemia. The difference peaked at day 18 (-46.8 in the 1400W treated group and -29.4 in the control group) and lasted until day 28. Histologic results were comparable with motor functional results. Histological observation revealed less axonal degeneration and earlier regeneration of nerve fibers in the 1400W treated rats than in the control rats. iNOS mRNA and protein were upregulated during the first 3 days of reperfusion, and iNOS inhibitor significantly attenuated the increased iNOS during the early phase of the reperfusion until 7days.
Conclusion: Inhibition of iNOS during the regeneration of the ischemic nerve influenced mRNA and protein level early in the reperfused period and assured faster functional recovery faster than in the untreated group. These results suggest that early administration of 1400W has therapeutic potential for the treatment of I/R injury.

목차 (Table of Contents)

• MATERIALS AND METHODS
• RESULTS
• DISCUSSION
• REFERENCES

참고문헌 (Reference)

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