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Monocrotaline 투여 백서 폐동맥 고혈압에서 폐혈관내피세포와 폐신경내분비 세포의 변화에대한 형태학적 연구

Authors
 양우익 
Department
 Dept. of Pathology (병리학교실) 
Issue Date
1991
Description
의학과/박사
Abstract

[영문] [한글] 폐동맥고혈압 발생에 중추적 역할을 하는 폐혈관내피세포의 변화를 관찰하여 monocrota line투여 폐동맥고혈압의 발생기전을 규명하고자, 자성 Wistar 백서 96마리를 대조군 24 마리와 menocrotaline 투여 실험군 72마리로 나누어 실험하였다. 실험군은 menocrotaline hydrochloride 2% 수용액 0.8cc(60mg/kg)를 1회 피하주사한 후 6시간, 12시간, 24시간, 36시간, 2일, 3일, 6일, 9일, 2주, 3주, 1달, 2달에 각기 6마리색 중류수 0.8cc를 투며한 대조군 2마리와 우심실의 수축기 압력을 측정하고 도살하였다. Hematoxylin-eosin 염색 에의한 일반적인 조직학적 변화외에 폐혈관내피세포의 von Willebrand factor 표현양상의 변화를 면역조직화학염색을 시행하여 관찰하였고,주로 초기변화를 규명하기 위하여 전자 현미경적 관찰을 시행하였고, 도살 1시간 전 꼬리정맥에 투여한 thymidine의 유사체인 5- bromo deoxyuridine을 이용하여 세포역동학연구를 시행하였다. 아울러 세포질내 신경과립에 혈관수축 작용이 있는 gastrin releasing peptide를 지녀 폐동맥고혈압의 발생기전에 관여할것으로 기대되는 폐신경내분비세포외 수적 변화를 gast rin releasing peptides에 대한 면역조직화학염색을 시행한 후 관찰하여 다음과 같은 결 과를 얻었다. 1. Monocrotaline 투여 3일 후부터 폐혈판내피세포가 폐혈관의 종류와 크기에 관계없이 von Willebrand factor에 대한 면역조직화학염색에 뚜렸한 염색상을 보이기 시작하였으 며, 이는 2달후까지 지속되었다. 2. 패소동맥 및 폐세동맥의 혈관내괴세포에 monocrotaline 투여 6시간 후부터 혈소한 및 염증세포의 부착이 관찰되기 시작하였으며, 24시간 후에는 혈소판의 탈자립 현상이 관 찰되었다. Monocrotaline 투여 12시간 후부터 미세구조상 myelin figure등 혈관내피세포 의 손상 소견이 관찰되기 시작하여 48시간 후 가장 뚜렸해졌다. Monocrotaline 투여 3일 추부터는 핵자 세포기능질의 비대소견이 관찰되기 시작하였으며 이는 2달까지는 지속되었 다. 3. Monocrotaline 투여 6일 후부터 폐소동맥 및 폐세동맥 혈관내피세포의 bromodeoxyur idine labeling index가 증가하기 시작하여 3주 후 최고치를 보였으나 1달과 2달 후에도 6∼9일 후의 수준으로 증가되어 유지되었다. 4. Gastrin releasing peptide에대한 면역조직화학염색상 양성인 폐신경내분비세포는 성숙된 백서 폐장에서는 거의 관찰할 수 없었으며, monocrotaline투여군에서도 증가하지 않았다. 이상의 결과로 monocrotaline 투여에 의한 폐고혈압은 초기 폐미세혈관 내피세포의 손 상, 혈소판 부착 및 활성화로 아마도 platelet derived growth factor가 유리되어 혈관내 피세포와 중막 평활근의 증식을 유발 지속시리고, 혈관내피세포의 기능장애에 의한 혈관 수축과 함께 혈관저항을 증가시켜 발생되는 것으로 사료된다. 폐신경내분비세포는 증가가 관찰되지않아 monocrotaline 투여에 의한 폐동맥고혈압의 발생기전에 관여하지 않을 것 으로 사료된다. A merphological study of the pulmonary endothelium and neuroendocrine cells in monocrotaline-induced pulmonary arterial hrpertension Woo-Ick Yang Department of Medical Science Tho Graduate School, Yonsei University (Directed br Professor In-Joon Choi, M.D.) The present study is aimed to investigate the changes of pulmonary endothelium which plays main role in the evolution of monocrotaline-induced pulmonary arterial hypertension and to understand the pathologic mechanism of pulmonary hypertension. Ninety-six female Wistar rats were divided into two groups-24 control animals and 72 experimental animals. The experimental animals were given a single subcutaneous injection of monocrotaline(0.8 cc of 2% monocrotaline) hydrochloride solution, 60 mg/kg) and the control animals were given an equivalent amount of saline(0.8 cc). Six animals from experimental group and two animals from control groups were sacrificed on the 6, 12, 24, 36, 48 hours and 3, 6, 9, 14, 21, 30, 60 days after monocrotaline injection following measurement of the right ventrirular systolic pressure. Besides the morphologic study of the pulmonary vaaculature with hematoxylin-eosin stain, we performed immunohistochemical study using antibody to von Willebrand factor, electronmicroscopic study mainly for detecting early ultrastructural changes and cell kinetic study using 5-bromodeoxyuridine injected intravenously 1 hours before the sacrifice of animals. In addition, we observed the changes in the number of pulmonary neuroendocrine cells containing gastrin releasing peptide, the potent vasoconstrictor, whether these cells may have some role in the menocrotaline induced pulmonary hypertension by immunohistochemical method using antibody to gastrin releasing peptide. In summary 1. The expression of von Willebrand factor by pulmonary endothelial cells wart markedly increased from day 3 until 2 months after monodcrotaline injection unrelated to the size and types of pulmonary vessels. 2. Attachment of inflammatory cells and platelets to endothelium was observed from 6 hours after monocrotaline injection and degranulatien of attached platelets occurs 24 hours after monocrotaline injection. From 12 hours after monocrotaline injection, ultrastructural evidences of endothetial injury, such as myelin figure, began to appear and was maximal after 48 hours. Ultrastructural changes of cell hypertrophy, such as nucleomegaly and increased cytoplasmic organelles, began to appear from day 3 and was continuously observed until 2 months after monocrotaline injection. 3. Six days after monocrotaline injection, the endothelium of small pulmonary arteries and arterioles began to show increased labeling index and it was maximal on the third week after monocrotaline injection. Thereafter the labeling index of endothelium was still maintained on the level of 6∼9 days after monocrotalin injection. 4. The pulmonary neuroendocrine cells, detected immunohistochemically using antibody to gastrin releasing peptide, were very rare in control group and they were not increased in experimental group. In conclusion the results indicate that pulmonary hypertensien by monocrotaline injection is due to increased vascular resistance caused by vasoconstriction and hyperplasia of endothelium with muscularization of the pulmonary arterioles induced by endothelial dysfuction and some biologic substanees, such as platelet derived growth factor and endothelium derived relaxation factor, released from damaged endethelium and attached platelets. The pulmonary neuroendocrine cells, showing no increase in number after monocrotaline injection, are considered to have no roles in the development of monocrotaline-induced pulmonary hypertension of Wistar rats at early stage.
Full Text
https://ymlib.yonsei.ac.kr/catalog/search/book-detail/?cid=CAT000000045359
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 3. Dissertation
Yonsei Authors
Yang, Woo Ick(양우익) ORCID logo https://orcid.org/0000-0002-6084-5019
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/135708
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