Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Contribution of Nociceptin to Alterations in Cerebral Blood Flow Regulation Following Postnatal Exposure to Ethanol in Rats

출생 초기 에탄올 투여 흰쥐의 뇌혈류 조절 변동에 대한 Nociceptin의 관여

  • Cho, Dong Hwan (Department of Pharmacology, Pusan National University School of Medicine) ;
  • Lee, Won Suk (Department of Pharmacology, Pusan National University School of Medicine)
  • 조동환 (부산대학교 의학전문대학원 약리학교실) ;
  • 이원석 (부산대학교 의학전문대학원 약리학교실)
  • Received : 2013.01.16
  • Accepted : 2013.01.24
  • Published : 2013.02.28
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Abstract

This study aimed to investigate whether nociceptin contributes to the alterations in cerebral blood flow (CBF) regulation following postnatal exposure to ethanol in Sprague-Dawley rats. Animals received ethanol twice a day, 2 hr apart, on postnatal 6, 7 and 8 days. The changes in regional CBF (rCBF) in response to the changes in mean arterial blood pressure were determined at 4-, 8-, and 12-week of age by laser-Doppler flowmetry. Hypotension was induced by the gradual withdrawal of blood from arterial catheter, and the reversal of blood pressure was produced by the reinfusion of blood. Expression of nociceptin-like immunoreactivity was determined in dura mater and cerebral cortex using immunohistochemistry. Postnatal exposure to ethanol almost abolished the autoregulation of rCBF in all age groups. Pretreatment with nociceptin but not with [$Nphe^1$]nociceptin(1-13)$NH_2$, a selective competitive nociceptin receptor antagonist, 5 min prior to ethanol administration preserved the autoregulation of rCBF in all age groups. Postnatal exposure to ethanol markedly increased the expressions of nociceptin-like immunoreactivity in the dura mater and cerebral cortex, both of which were significantly inhibited by pretreatment with 7-nitroindazole monosodium salt as well as aminoguanidine 5 min prior to ethanol administration in all age groups. The values of arterial blood gas analysis were not significantly different from the basal levels in all groups. These results suggest that nociceptin deeply contributes to the compensatory mechanisms for the nitric oxide-dependent alterations in CBF autoregulation following postnatal exposure to ethanol.

본 연구는 Sprague-Dawley계 숫쥐에서 출생 초기 에탄올에의 노출에 의한 성장 후 뇌혈류 자가조절의 변동을 관찰하고 이러한 변동에 대한 nociceptin의 관여를 관찰하고자 하였다. 실험동물에게 에탄올 2.5 g/kg을 생후 6, 7 및 8일의 3일 동안 2시간 간격으로 1일 2회 피하 주사하였다. 주령 4, 8 및 12주 시기에 단계적 출혈에 의한 저혈압 및 혈액 재주입에 의한 혈압 상승시의 평균동맥혈압의 변동에 따른 국소 뇌혈류 변동을 laser-Doppler flowmetry 방법으로 측정하였고, 경막과 대뇌피질에서 nociceptin-유사 면역반응력의 발현을 면역조직화학법으로 측정하였다. 출생 초기 에탄올 투여는 4, 8 및 12주령 모두에서 국소 뇌혈류 자가조절 기능을 거의 소실시켰다. 에탄올 투여 전에 nociceptin을 전처치한 군에서는 모든 연령군에서 국소 뇌혈류 자가조절 기능이 보존되었으나, nociceptin 수용체 선택적 경쟁적 길항제인 [$Nphe^1$]nociceptin(1-13)$NH_2$를 전처치한 군에서는 보존되지 아니하였다. 출생 초기 에탄올 투여에 의하여 경막 내 nociceptin-유사 면역반응력이 모든 연령군에서 현저히 증가하였고, 7-nitroindazole (7-NINA) 전처치뿐만 아니라 aminoguanidine 전처치에 의하여 모든 주령에서 유의하게 억제되었다. 출생 초기 에탄올 투여에 의하여 대뇌피질 내 nociceptin-유사 면역반응력이 모든 연령군에서 현저히 증가하였고, 7-NINA 전처치와 aminoguanidine 전처치에 의하여 모든 주령에서 유의하게 억제되었다. 모든 실험군의 동맥혈가스분석 결과는 실험 전, 중 및 후에 유의한 차이를 보이지 아니하였다. 이상의 결과로 보아 출생 초기 에탄올 투여는 성장 후 뇌혈류 자가조절에 변동을 초래하고, 이에 대한 보상기전으로서 nociceptin의 발현이 증가하는데, 여기에는 nitric oxide가 깊이 관여하는 것으로 생각된다.

Keywords

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