Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
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태아 백서에서 임신 백서의 자궁 내 대동맥 결찰로 유발한 뇌실주위 백질연화증

Periventricular leukomalacia induced by in utero clamping of pregnant rat aorta in fetal rats

  • 장윤실 (성균관대학교 의과대학 삼성서울병원 소아과청소년과) ;
  • 성동경 (삼성생명과학연구소) ;
  • 강샘 (삼성생명과학연구소) ;
  • 박수경 (성균관대학교 의과대학 삼성서울병원 소아과청소년과) ;
  • 정유진 (성균관대학교 의과대학 삼성서울병원 소아과청소년과) ;
  • 서현주 (성균관대학교 의과대학 삼성서울병원 소아과청소년과) ;
  • 최서희 (성균관대학교 의과대학 삼성서울병원 소아과청소년과) ;
  • 박원순 (성균관대학교 의과대학 삼성서울병원 소아과청소년과)
  • Chang, Yun Sil (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea) ;
  • Sung, Dong Kyung (Samsung Biomedical Research Institute) ;
  • Kang, Saem (Samsung Biomedical Research Institute) ;
  • Park, Soo Kyung (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jung, Yu Jin (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Seo, Hyun Joo (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Choi, Seo Heui (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Park, Won Soon (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 투고 : 2008.05.14
  • 심사 : 2008.07.21
  • 발행 : 2008.08.15
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초록

목 적 : 본연구의 목적은 자궁 내 태아 백서에서 임신 백서의 대동맥 결찰로 허혈증을 유발하여 뇌실주위 PV) 유발 동물실험 모델을 개발하고자 하는 데 있다. 방 법 : 임신일령 21일 분만 직전 상태의 Sprague-Dawley rat를 진정 및 마취시킨 후 소동물용 하바드 인공호흡기를 사용하여 인공호흡을 시행하였고 이후 개복술을 실시하여 수술 겸자로 대동맥을 40분 동안 가역적으로 결찰 하였고, 이후 제왕절개술로 태아백서를 분만하고 인공호흡 등의 심폐소생술을 시행하여 안정화된 후 대리모에서 자라도록 하여 생후 21일에 뇌조직의 검체를 얻었다. 뇌조직의 검체는 관류한 후 고정하여 $10{\mu}m$ 두께의 연속 절편을 만들어서 병리학적 소견과 뇌실확장(ventriculomegaly) 여부를 관찰하였다. 뇌실확장의 정도는 각 연속 절편에서 측정한 전체 뇌 용량에 대한 뇌실용량의 비율로 판단하였다. 결 과 : 임신 백서에서 대동맥 결찰로 자궁 내 허혈증 유발 후 11마리의 태아 백서 중 8마리(73%)의 태아백서가 심폐소생술 시행 후 생존 하였고 정상 대조군은 10마리 모두 생존하였으며 생후 21일에 측정한 체중과 뇌의 중량 모두 허혈군에서 정상 대조군 보다 더 유의하게 감소되었다. 병리학적 소견 상 뇌조직의 연속 절편에서 측정한 뇌실용적의 비율은 허혈군에서 대조군보다 유의하게 증가하여($3.67{\pm}1.21%$ vs. $0.23{\pm}0.06%$) 뇌실 확장이 관찰되었으며 뇌조직의 낭성 병변은 관찰되지 않았으나 뇌조직의 희박화(rarefaction)는 6례에서는 경도로, 2례에서는 중등도로 관찰되었다. 결 론 : 자궁 내 태아백서에서 임신백서의 대동맥 결찰로 허혈증을 유발하여 PVL 유발 동물실험 모델을 개발할 수 있었다.

Purpose : This study was undertaken to develop an animal model of periventricular leukomalacia (PVL) induced by in utero clamping of pregnant rat aorta in fetal rats. Methods : A timed pregnanct Sprague-Dawley rat on embryonic day 21 just prior to delivery was sedated and anesthetized, and a Harvard ventilator for small animals was applied. Following laparotomy, the maternal aorta was clamped reversibly for 40 minutes using a surgical clip. The fetal rats were then delivered by Cesarean section, resuscitated if necessary, and reared by a surrogate mother rat until postnatal day 21 to obtain the brain specimen. After systemic perfusion and fixation, $10{\mu}m$ thick serial brain sections were obtained and stained for pathologic examination and assessment of ventriculomegaly. Ventriculomegaly was assessed by the measured ventricle to total brain volume ratio. Results : Eight out of eleven fetal rats (73%) survived in the ischemia group after induction of in utero ischemia by clamping maternal rat aorta, and all ten survived in the control group. Body and brain weights measured at postnatal day 21 were significantly lower in the ischemia group compared to the control group. In pathologic findings, significant ventriculomagaly ($3.67{\pm}1.21%$ vs. $0.23{\pm}0.06%$) was observed in the ischemia group compared to the control group; although cystic lesion was not observed, mild (n=6) and moderate (n=2) rerefaction of the brain tissue was observed. Conclusion : A fetal rat model of PVL induced by in utero clamping of pregnant rat aorta was developed.

키워드

과제정보

연구 과제 주관 기관 : Korea research foundation

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