허혈성 대뇌손상시 curcumin 투여에 의한 peroxiredoxin-5 발현의 변화
Change of Peroxiredoxin-5 Expression by Curcumin Treatment in Cerebral Ischemia
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Curcumin은 항산화제로서 신경세포의 보호작용에 관여하며, peroxiredoxin-5는 활성산소의 형성을저해하여 산화적 스트레스로부터 신경세포를 보호한다고 알려져 있다. 본 연구는 허혈성 대뇌손상모델에서 curcumin에 의해 조절되는 peroxiredoxin-5 발현의 변화에 관하여 조사하였다. 실험동물은 흰쥐(Sprague-Dawley, 수컷)를 사용했으며, 허혈성 대뇌손상을 유도하기 위하여 중간대뇌동맥폐쇄술(MCAO)을 실시하였다. MCAO를 시행한 1시간 후에 curcumin(50㎎/㎏ B.W.) 또는 vehicle을 복강으로주사하였고, MCAO을 실시한 24시간 후 대뇌피질의 조직을 적출하였다. Hematoxylin과 eosin 조직염색 결과 MCAO를 시행한 대뇌피질에서는 신경세포의 괴사 소견을 보였지만, curcumin 투여군에서 이들 신경세포의 손상이 완화되어 있어 MCAO로 유도된 대뇌 손상시 curcumin의 보호효과를 확인하였다. 또한 MCAO를 실시한 vehicle+MCAO 실험군에서 peroxiredoxin-5 단백질의 발현은 감소하였으나, curcumin을 처리한 curcumin+MCAO 실험군에서는 vehicle+MCAO 실험군의 감소에 비해 감소의폭이 현저히 줄어들어 MCAO를 시행하지 않은 sham군의 발현 수준으로 유지되었다. ReversetranscriptionPCR과 Western blot 분석을 통해 중간대뇌동맥폐쇄술로 유도된 허혈성 대뇌손상 모델에서 peroxiredoxin-5 발현의 감소와 curcumin의 투여에 의한 peroxiredoxin-5 발현 감소의 완화를 확인하였다. 본 연구의 결과는 curcumin의 처리는 MCAO로 인한 peroxiredoxin-5 발현의 감소를 억제시킨다는 것을 보여주었다. 따라서, 대뇌손상 모델동물에서 curcumin은 MCAO로 유도된 peroxiredoxin-5발현의 감소 정도를 완화시킴으로서 curcumin이 신경세포 보호작용에 기여하는 것으로 사료된다.
Abstract
Curcumin plays a protective role in brain injury through its anti-oxidant and anti-inflammatoryactivities. Moreover, peroxiredoxin-5 exerts a protective effect against oxidative stress. The aimof this study was to investigate whether curcumin modulated the peroxiredoxin-5 expression infocal cerebral ischemic animal model. Middle cerebral artery occlusion(MCAO) was performedto induce cerebral ischemic injury in rats. Adult male rats were injected intraperitoneally withvehicle or curcumin(50㎎/㎏ B.W.) 1 h after MCAO and cerebral cortex tissues were collected24 h after MCAO. Photographs of hematoxylin and eosin staining showed that MCAO inducednecrotic changes with scalloped shrunken form and apoptotic changes with nuclear chromatin condensations. However, curcumin treatment attenuated MCAO-induced histopathological changes. Moreover, this study clearly showed that peroxiredoxin-5 expression was decreased in MCAOoperated animal with vehicle using a proteomics approach. However, this decrease inperoxiredoxin-5 expression was attenuated by curcumin treatment. Reverse-transcription PCR andWestern blot analyses confirmed that curcumin treatment alleviated the MCAO injury-induceddecrease in peroxiredoxin-5 . These results demonstrated that curcuminregulates peroxiredoxin-5 expression in MCAO animal model. In conclusion, our findings suggestthat curcumin exerts a neuroprotective effect in cerebral ischemia by attenuating theMCAO-induced decrease in peroxiredoxin-5 expression.
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