{"title":"瑞西瓜特能改善SU5416诱导的大鼠支气管肺发育不良实验模型。","authors":"Shinichi Katsuragi, Hidekazu Ishida, Hidehiro Suginobe, Hirofumi Tsuru, Renjie Wang, Chika Yoshihara, Atsuko Ueyama, Jun Narita, Ryo Ishii, Shigetoyo Kogaki, Keiichi Ozono","doi":"10.1080/01902148.2021.1976311","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature neonates. Classical BPD is caused by hyperoxia and high-pressure mechanical ventilation, whereas BPD in recent era is caused by impaired pulmonary angiogenesis and alveolarization in extreme prematurity. Although sildenafil was reported to be effective in a hyperoxia-induced rat BPD model, several clinical trials could not demonstrate any significant improvement in the respiratory statuses of BPD infants. Riociguat is a soluble guanylate cyclase stimulator that increases cyclic guanosine monophosphate activity in a nitric oxide independent manner. However, a beneficial effect in BPD has not been established yet.</p><p><strong>Methods and results: </strong>We established BPD model in rats by injection of SU5416 on day 1 followed by maintenance under normoxia, which resulted in oversimplified alveoli, sparse pulmonary capillary vessels, severe pulmonary hypertension, and growth retardation, which mimicked the features observed in recent clinical management of BPD. We administered riociguat from day 10, when BPD rats exhibited growth retardation. Histological analyses demonstrated that riociguat treatment significantly but partially ameliorated lung alveolarization, vascularization, and pulmonary hypertension. However, the survival rate was not significantly improved by riociguat treatment.</p><p><strong>Conclusions: </strong>Riociguat could ameliorate pulmonary alveolarization, vascularization, and hypertension in the SU5416 induced BPD rat model, but could not improve the overall survival.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"47 8","pages":"382-389"},"PeriodicalIF":1.5000,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Riociguat can ameliorate bronchopulmonary dysplasia in the SU5416 induced rat experimental model.\",\"authors\":\"Shinichi Katsuragi, Hidekazu Ishida, Hidehiro Suginobe, Hirofumi Tsuru, Renjie Wang, Chika Yoshihara, Atsuko Ueyama, Jun Narita, Ryo Ishii, Shigetoyo Kogaki, Keiichi Ozono\",\"doi\":\"10.1080/01902148.2021.1976311\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature neonates. Classical BPD is caused by hyperoxia and high-pressure mechanical ventilation, whereas BPD in recent era is caused by impaired pulmonary angiogenesis and alveolarization in extreme prematurity. Although sildenafil was reported to be effective in a hyperoxia-induced rat BPD model, several clinical trials could not demonstrate any significant improvement in the respiratory statuses of BPD infants. Riociguat is a soluble guanylate cyclase stimulator that increases cyclic guanosine monophosphate activity in a nitric oxide independent manner. However, a beneficial effect in BPD has not been established yet.</p><p><strong>Methods and results: </strong>We established BPD model in rats by injection of SU5416 on day 1 followed by maintenance under normoxia, which resulted in oversimplified alveoli, sparse pulmonary capillary vessels, severe pulmonary hypertension, and growth retardation, which mimicked the features observed in recent clinical management of BPD. We administered riociguat from day 10, when BPD rats exhibited growth retardation. Histological analyses demonstrated that riociguat treatment significantly but partially ameliorated lung alveolarization, vascularization, and pulmonary hypertension. However, the survival rate was not significantly improved by riociguat treatment.</p><p><strong>Conclusions: </strong>Riociguat could ameliorate pulmonary alveolarization, vascularization, and hypertension in the SU5416 induced BPD rat model, but could not improve the overall survival.</p>\",\"PeriodicalId\":12206,\"journal\":{\"name\":\"Experimental Lung Research\",\"volume\":\"47 8\",\"pages\":\"382-389\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2021-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental Lung Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/01902148.2021.1976311\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2021/9/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Lung Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/01902148.2021.1976311","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/9/16 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
Riociguat can ameliorate bronchopulmonary dysplasia in the SU5416 induced rat experimental model.
Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature neonates. Classical BPD is caused by hyperoxia and high-pressure mechanical ventilation, whereas BPD in recent era is caused by impaired pulmonary angiogenesis and alveolarization in extreme prematurity. Although sildenafil was reported to be effective in a hyperoxia-induced rat BPD model, several clinical trials could not demonstrate any significant improvement in the respiratory statuses of BPD infants. Riociguat is a soluble guanylate cyclase stimulator that increases cyclic guanosine monophosphate activity in a nitric oxide independent manner. However, a beneficial effect in BPD has not been established yet.
Methods and results: We established BPD model in rats by injection of SU5416 on day 1 followed by maintenance under normoxia, which resulted in oversimplified alveoli, sparse pulmonary capillary vessels, severe pulmonary hypertension, and growth retardation, which mimicked the features observed in recent clinical management of BPD. We administered riociguat from day 10, when BPD rats exhibited growth retardation. Histological analyses demonstrated that riociguat treatment significantly but partially ameliorated lung alveolarization, vascularization, and pulmonary hypertension. However, the survival rate was not significantly improved by riociguat treatment.
Conclusions: Riociguat could ameliorate pulmonary alveolarization, vascularization, and hypertension in the SU5416 induced BPD rat model, but could not improve the overall survival.
期刊介绍:
Experimental Lung Research publishes original articles in all fields of respiratory tract anatomy, biology, developmental biology, toxicology, and pathology. Emphasis is placed on investigations concerned with molecular, biochemical, and cellular mechanisms of normal function, pathogenesis, and responses to injury. The journal publishes reports on important methodological advances on new experimental modes. Also published are invited reviews on important and timely research advances, as well as proceedings of specialized symposia.
Authors can choose to publish gold open access in this journal.