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

脳内アンジオテンシンIIの細胞内局在,生合成ならびに放出機構と高血圧発症との関連

血管紧张素II在脑内的细胞内定位、生物合成和释放机制与高血压发生的关系

基本信息

批准号：
01570500
负责人：
水野兼志
金额：
$ 1.34万
依托单位：
Fukushima Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

(1)高血圧自然発症ラット(SHR)ならびに対照ラット(WKY)の脳内アンジオテンシンIIの局在性の検討:生後16週齢のSHRおよびWKYをそれぞれペントバルビタ-ル麻酔下に断頭屠殺し,直ちに脳より視床,視床下部および中脳を摘出し,そのホモジネイトからアンジオテンシンII(AII)分画を抽出して後,ラジオイムノアッセイ法により測定した。その結果,AIIはSHRおよびWKYとも中脳が最も高く,次いで視床下部および視床の順であった。脳内AIIは,いずれの分画ともWKYがSHRに比し高値の傾向を示した(中脳,SHR=104pg/g tissue,WKY=144pg/g tissue;視床下部,SHR=83pg/g tissue,WKY=116pg/g tissue;視床,SHR=69pg/g tissue,WKY=96pg/g tissue)。次いで,生後10〜12週齢のSHRならびにWKYの脳から中脳を摘出し,これを2×2mm大の組織片としてKrebsーRinger液(37℃,95%O_2,5%CO_2存在下)中に1〜2時間組織培養し,培養液中のアンジオテンシンI(AI)ならびにAIIを測定したところ,AIはSHRおよびWKYとも培養液中に検出された(それぞれ5〜10pg)が,AIIはともに検出されなかった。この理由として,実験に供した動物の週齢が関与すると思われるので,今後はさらに幼若ラット(生後1〜2日)を用いて検討する必要がある。(2)脳内AIIの放出機序の検討:生後10〜12週齢のSHRの脳から(1)と同様に中脳を組織培養し,培養液中にカルシウムイオノフォア(A23187,10μM)を添加したところ,AII測定感度(1pg/tube)以下の低値から添加1時後に6〜8pgに上昇した。一方,培養液中にホルボ-ルエステル(TPA,0.5〜1μM)を添加してAIIの放出の有無を検討したところ,AIIの放出は認められなかった。今後,SHRおよびWKYとも幼若のものを用いて,AI,AII放出の程度とその機序について検討する必要があると考えられる。

(1)The present study of spontaneous hypertension syndrome II (SHR) and WKY: SHR and WKY at 16 weeks after birth were divided into two groups: the first group was killed under anesthesia, the second group was killed under anesthesia, the third group was killed under anesthesia, the fourth group was killed under anesthesia, the fourth group was killed under anesthesia, and the fourth group was killed under anesthesia. As a result,AII is the highest in SHR and WKY, and the second is the lower part of the viewing bed. AII in the middle showed a tendency for SHR to be higher than WKY (middle,SHR=104pg/g tissue,WKY=144 pg/g tissue; lower optic bed,SHR=83pg/g tissue,WKY=116pg/g tissue; optic bed,SHR=69pg/g tissue,WKY=96pg/g tissue). At 10 ~ 12 weeks after birth, SHR and WKY were harvested and cultured in Krebs Ringer solution (37℃, 95%O_2, 5%CO_2) for 12 hours. The AII was detected in SHR and WKY culture solution (5 ~ 10pg). The reason for this is that it is necessary to discuss the animal's life cycle and thoughts in the future if it is young (1 ~ 2 days after birth). (2)A study of the release mechanism of AII in SHR at 10 ~ 12 weeks after birth was carried out. When A23187 (10μM) was added to the culture medium, the sensitivity of AII was measured at a low value below 1pg/tube, and increased at 6 ~ 8pg after 1 hour of addition. In addition, the presence or absence of AII release was investigated in culture medium containing TPA (0.5 ~ 1μM). From now on,SHR and WKY will be used in the future. The degree of AI and AII emission and the mechanism of AII emission will be discussed.