权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

肝移植後の各種病態における低分子モノオキシド代謝の解析と制御、治療への応用

肝移植后各种病理状态下低分子一氧化碳代谢的分析与控制及其在治疗中的应用

基本信息

批准号：
10877186
负责人：
土肥雪彦
金额：
$ 1.22万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Exploratory Research
财政年份：
1998
资助国家：
日本
起止时间：
1998 至无数据
项目状态：
已结题

项目摘要

低分子ガス情報伝達物質であるnitric oxide(NO),carbon monoxide(CO)は,生体内で非常に不安定であり,特に移植臓器内での動態解析は困難であった。我々はラット肝移植において,近赤外分光法によりNO代謝産物であるnitrosyl-Hbを測定し,虚血再灌流障害,拒絶反応における臓器内NO酸素代謝を測定した。同系肝移植において虚血再灌流,特に冷保存再潅流では,活性化したKupffer細胞,マクロファージからNOが産生される可能性を検討したところ,UW液による冷保存24時間群のnitrosyl-Hbレベルが再灌流後2時間より著明に上昇し,3日以降正常に復した。次いで拒絶反応におけるNOの動態を同種移植を用いて検討した。無治療群では3日目の急性拒絶反応早期よりnitrosyl-Hbが上昇し,次いでoxidized-Cyt.aa3,oxy-Hbの値が有意な低値を示した。しかしデオキシスパーガリン治療群ではその変化は抑制された。以上の近赤外分光データと病理組織所見とを対比して検討したところ、門脈領域への単核細胞の浸潤が始まる移植移3日目からnitrosyl-Hbレベルが上昇し,この浸潤が実質に波及する6日目にはoxidized-Cyt.aa3が低下し,肝細胞壊死の著明となる8日目に,はoxy-Hbが有意に低下した。すなわち移植肝組織内nitrosyl-Hbレベルの推移は単核細胞浸潤の程度を,oxidized-Cyt.aa3,oxy-Hbレベルは拒絶にともなう肝実質組織障害の程度をよく反映し,拒絶反応のモニタリングとして有用と考えられた。更に我々は本法が含気臓器である肺に応用可能であることを証明し,測定プローベの改良により大型動物を用いた経肋骨体外測定システムを開発した。

Low molecular weight (LMWH) is sensitive to nitric oxide (NO), carbon monoxide (CO), which is very unstable in vivo, so it is difficult to analyze the dynamics in the transplant. We do not know if there is any damage to the liver transplantation, we should use the near-infrared spectroscopy to determine the NO substitute, the nitrosyl-Hb test, the deficiency blood reperfusion barrier, and reject the NO acid substitution test in the device. After orthotopic liver transplantation, hypovolemic blood was reperfused, cryopreserved and reperfused, Kupffer cells were activated, NO cells were activated, NO cells were incubated in cold storage for 24 hours, and nitrosyl-Hb cells were cryopreserved for 24 hours. After reperfusion, the samples were stored for 2 hours, and the normal temperature was reduced for 3 days. In the second place, you will not be allowed to use the same kind of transplant for the same type of NO. There is no cure group for 3 days. In the early stage, there is an acute rejection on the nitrosyl-Hb, and the secondary oxidized-Cyt.aa3,oxy-Hb is intended to show a low level. Let's talk about how to treat a group of people. The histopathological findings of the histopathology were much higher than those seen in the histopathological examination, and the nitrosyl-Hb cells in the field were significantly lower than those in the histopathology. at the beginning of the transplantation, 3 days after the transplantation, the oxidized-Cyt.aa3 was affected on the 6th day, the liver cell died on the 8th day, and the oxy-Hb was intentionally low on the 8th day. The degree of nuclear cytophagy was affected by the increase of nitrosyl-Hb concentration in the tissue of liver transplantation, and the degree of tissue damage was reflected by oxidized-Cyt.aa3,oxy-Hb response. In this method, it is possible to determine the mechanical properties of large animals by using the rib ribs in vitro.