| Project/Area Number |
17591862
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatric surgery
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| Research Institution | OSAKA UNIVERSITY |
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Principal Investigator |
KAMATA Shinkichi Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (40161202)
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| Co-Investigator(Kenkyū-buntansha) |
USUI Noriaki Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (30273626)
KANGAWA Kenji National Cardiovascular Center Research Institute, Department of Biochemistry, Director, 生化学部, 部長 (00112417)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | congenital diaphragmatic hernia / adrenomedullin / gene therapy / pulmonary hypoplasia |
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| Research Abstract |
Background/Purpose : While the prognosis in congenital diaphragmatic hernia (CDH) with hypoplastic lung is still poor in spite of recent progress of the therapy, lung growth in the period of fetus and newborn has been thought to be more important. Preliminary study indicated that adrenomedullin (AM) increased branching morphogenesis in a nitrophen-treated rat model of CDH. In this study, we examined an effect of AM gene transfer on growth of the lung in a rabbit model of CDH.
Methods : Left-sided congenital diaphragmatic hernia was surgically created in fetuses of timed-pregnant New Zealand white rabbits on day 24 of gestation (term: 31 days). In control animals, laparotomy was performed on day 24 of gestation. Positively charged biodegradable gelatin was used to produce ionically linked DNA-gelatin complex that could delay DNA degradation. After an incision of the left diaphragm, experimental animals were underwent tracheal injection of AM DNA gelatin complex (AM-gelatin group), gelatin (gelatin group) and saline (saline group).
Results : On day f 30 of gestation, lung-to-body weight ratio in AM gelatin group was significantly higher than that in gelatin and saline group, though that was significantly lower than that in controls. Pulmonary AM in AM gelatin group was significantly increased as compared to that in gelatin, saline and control group. Immunohistochemistry in AM gelatin group indicated strong staining of AM in the airway cells and vascular cells. AM m-RNA also increased in AM gelatin group.
Conclusion : AM gene transfer induced therapeutic effects in a rabbit model of congenital diaphragmatic hernia.
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