実験的温阻血腎における尿および腎組織中γ-GTPの研究

Abstract

正常雑種成犬を用いて実験的に30分間の温阻血腎を作成し, 阻血解除後の尿中のγ-GTP活性値を経時的に測定することにより近位尿細管の機能および病態について検討した.また同時に, 腎皮質中のγ-GTP活性および病理組織所見についても検索をした.1) γ-GTPは腎皮質中に多量に活性を認め, 髄質値の約4倍, 肝値の約45倍であった(p<0.005).2)温阻血解除後γ-GTPは血流側へ流入することなく尿中へ逸脱, 分泌されるが, 速やかに正常値に復する傾向を示した.3)温阻血解除後, 皮質中のγ-GTP活性値は経時的に上昇し, 3時間群5腎で最高値を示した(p<0.01)が, 5時間群12腎では正常に復する傾向を示した.4)温阻血を5時間まで継続した8腎においてその皮質および髄質中のγ-GTP活性値は経時的変化を示すことはなかった.γ-GTPは少なくとも5時間の虚血状態下でも不活性化されない安定な物質であることと, 虚血継続状態下では腎のviabilityは示されないことが判明した.5)光顕的には30分間の温阻血は近位尿細管に対して形態的および量にしてごく軽微な変化しか影響を及ぼさなかったが, 一部では進行性であった.6)利尿が得られなかった7腎は温阻血前すでに尿中γ-GTP活性値の高値または異常高値が認められ, 本実験操作による阻血が腎機能の状態をさらに増悪したためだと考えられた.7)尿中のγ-GTP活性値の経時変動は近位尿細管の機能および病態をよく反映し, その回復過程を示すマーカーの1つになりうると考えられた

The acute changes of proximal tubule function and its pathological condition were investigated by measuring (gamma-GTP) activities in the urine and renal tissue using warm ischemic kidneys of adult dogs (n = 34). Eight kidneys were kept in a warm ischemic condition throughout the experimental period and the tissue was extirpated from the kidney at every hour, and 31 kidneys were released from the 30 min ischemic condition. The urine and the blood (peripheral and renal artery and vein) were collected from these kidneys at every hour up to 5 hr. The kidneys observed for urine outflow (n = 24) were divided into three groups with time; 7 kidneys (1 hr), 5 kidneys (3 hr), and 12 kidneys (5 hr), and they were extracted. The gamma-GTP activity of the urine showed the maximum value of 851 +/- 102 mIU/ml at 30 min and decreased to 217 +/- 56 mIU/ml, which declined to be close to the starting value of 133 +/- 26 mIU/ml, at 5 hr after the warm ischemic condition was released. The gamma-GTP activities of the cortex were 325 +/- 62 mIU/mg.p (1 hr), 527 +/- 37 mIU/mg.p (3 hr), and 266 +/- 44 mIU/mg.p (5 hr). However, no increase in gamma-GTP activity was observed either in the renal vein blood, or in the cortex obtained from the 8 kidneys kept in the warm ischemic condition. A histopathological examination showed the progressive changes in some parts of the proximal tubules after release from the ischemic condition.(ABSTRACT TRUNCATED AT 250 WORDS)