類洞および類洞内皮細胞の形態変化からみた門脈血行動態と肝再生

从肝窦及肝窦内皮细胞形态变化角度探讨门静脉血流动力学与肝再生

• 批准号: 07770145
• 负责人: 南條 博
• 金额: $ 0.45万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Encouragement of Young Scientists (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07770145/
• 关键词: 類洞; 類洞内皮細胞; 門脈血行動態; 肝再生; 門脈循環; 血流調節; マイトマイシンC; 血管新生

肝疾患の病態を考える上で門脈循環は重要であり、近年肝臓自体による血流調節が注目されている.本研究は、肝血管床で最大の類洞および類洞内皮細胞の形態変化が門脈血行動態へ及ぼす影響を明らかにするため、肝再生を肝細胞増生に連動する類洞の血管新生と考え以下の実験を施行した.(方法)Mitomycin C (MMC)がもつ血管内皮細胞再生抑制と血管新生抑制作用を用い、MMCの一回門脈内投与後、ラット70%肝部分切除を行ない、切除肝の再生過程における肝内血管形態、門脈血行動態の変化を生理食塩水門脈投与群と比較検討した.体重300g前後の10週齢,SD系雄ラット50匹を用いた。MMC0.5mg/kg、1.0mg/kg、生理食塩水1.0mg/kgの三種類の門脈内投与群を設定(各群15匹ずつ)、sham operationを施した5匹を対照とした.MMCないし生理食塩水を門脈内投与後に70%肝部分切除を施行、術後1、2、4週後に再開腹(各群各日5匹ずつ)し、門脈血行動態の計測と、肝内血管形態の検討として3%グルタールアルデヒドによる門脈等圧灌流固定による光顕、透過電顕、走査電顕による検討を行った.(結果)1)肝重量、肝重量/体重比;1、2週後でMMC投与群は生食投与群より有意に低かったが、4週後では有意差はなかった.2)門脈血行動態;肝切除直後、門脈血流量は60%減少、門脈圧は50%上昇、以後肝重量の回復に伴い切除前値に戻る傾向を示した.しかし1、2週後でMMC投与群は生食投与群に比べそれが遅延した.4週後では有意差はなかった.3)1週後のMMC投与群で類洞配列の乱れと、腫大、核融解、偽封入体などの類洞内皮細胞の変性、壊死が目立った.4週後のMMC投与群の類洞形態は生理食塩水群と差がなかった.(考察)類洞内皮細胞の障害が類洞形態の乱れと類洞新生の遅延、肝微小循環障害を惹起し、肝再生遅延に至ったと考えられる.類洞および類洞内皮細胞の形態変化は門脈循環と密接に関連している.

Liver disease and pathological examination of the portal circulation is important, in recent years, liver self-regulation of blood flow is concerned. This study was conducted to investigate the effects of morphological changes of the largest cavity-like endothelial cells in the hepatic vascular bed on portal blood circulation and angiogenesis. (Methods)Mitomycin C (MMC) was used to inhibit vascular endothelial cell regeneration and angiogenesis. After MMC was administered into portal vein, 70% partial hepatectomy was performed. The changes of intrahepatic vascular morphology, portal blood circulation and group were compared. 10 weeks after weighing 300g,SD is male and 50 is female. MMC 0.5 mg/kg, 1.0 mg/kg, physiological water 1.0 mg/kg three kinds of intraportal administration and group settings (each group 15 points), sham operation to apply to 5 points contrast to the next.MMC to physiological water intraportal administration and 70% partial hepatectomy, 1, 2, 4 weeks after surgery again laparotomy (5 days for each group), measurement of portal blood flow, examination of intrahepatic vascular morphology, and examination of light, electricity, and trace electricity. (Results)1) Liver weight, liver weight/body weight ratio;1, 2 weeks after MMC administration and group feeding, group feeding and group feeding, intentionally low; 4 weeks after MMC administration and group feeding, intentionally low; 2) Portal blood flow; After hepatectomy, portal blood flow decreased by 60%, portal blood pressure increased by 50%, and liver weight recovered later, accompanied by a tendency to decrease before hepatectomy. After 1 or 2 weeks, MMC administration and group feeding were delayed. After 4 weeks, MMC administration and group feeding were delayed. 3) After 1 week, MMC administration and group feeding were delayed. After 4 weeks, MMC administration and group feeding were delayed. After 4 weeks, MMC administration and group feeding were delayed. (Investigation) The damage of cavity-like endothelial cells, the disorder of cavity-like morphology, the delay of cavity-like regeneration, the initiation of liver microcirculation damage, the delay of liver regeneration, and the investigation of cavity-like morphology. The morphological changes of cavity-like endothelial cells are related to portal circulation and close junction.