Departmental Bulletin Paper 糖尿病ラット腎臓の低灌流-再灌流障害に対するノルエピネフリンとグリベンクラミドの効果
Effects of Norepinephrine and/or Glibenclamide on Underperfusion-Reperfusion Injuries in Kidneys Isolated from Normal and Diabetic Rats

古堅, 裕章  ,  樋口, マキヱ

Description
 先行研究にて、非糖尿病心臓に比べ糖尿病心臓は低灌流-再灌流障害を受けやすく、この障害はノルエピネフリンで増悪し、そこに血糖降下薬グリベンクラミドが存在するとさらに悪化することが明らかになっている。腎臓においてもこれらの障害や増悪が心臓と同様に起こりうる可能性があると考えられる。本研究では、ストレプトゾトシン誘発糖尿病ラット摘出灌流腎臓の低灌流-再灌流障害に対するノルエピネフリンおよびグリベンクラミドの効果を腎灌流圧、腎灌流量、尿量の変化から比較検討した。1)糖尿病腎臓は非糖尿病腎臓と比べ、通常灌流時の尿量は多いが次第に減少し、低灌流時の減少度は大きく、再灌流時の回復度は悪かった。また、再灌流時の灌流圧の上昇は糖尿病腎臓で大きかった。2)ノルエピネフリン10-7M による腎灌流圧の上昇は、糖尿病腎臓の方が大きかったが、尿量の回復度には影響なかった。3)グリベンクラミド10-6M により、低灌流-再灌流障害は影響されなかった。4)ノルエピネフリン存在下のグリベンクラミドにより、糖尿病腎臓の低灌流- 再灌流障害は影響されなかったが、非糖尿病腎臓の再灌流時の灌流圧上昇は増強された。これらのことから、心臓と同様に糖尿病腎臓の方が低灌流-再灌流障害を受けやすいが、ノルエピネフリン10-7M およびグリベンクラミド10-6M の濃度は、低灌流-再灌流障害による尿量の減少には影響を与えないことが明らかになった。ノルエピネフリンやグリベンクラミドの血管平滑筋収縮による、灌流圧の上昇は低灌流- 再灌流障害の尿量の変化に影響がないようであり、糖尿病腎臓ではKATP チャネル開口による低灌流障害の保護の役割は低い可能性が示唆された。  Previous studies have shown diabetic hearts to be more susceptible than non-diabetic hearts to coronary perfusion flow reduction. The studies show that norepinephrine (NE) exacerbated this effect, particularly in diabetic hearts, and did so more rapidly in the presence of Glibenclamide (Glyb). The purpose of this study was to consider whether injuries and exacerbation can be caused equally in the kidney. Changes in the renal perfusion pressure (RPP),renal perfusion flow (RPF), and urine flow (UF) were examined during normal perfusion, underperfusion, and reperfusion with NE and/or Glyb in isolated perfused non-diabetic and streptozotocin-induced diabetic rat kidneys. 1)The UF during normal perfusion was greater but began to decrease gradually, the rate of decrease in the UF during underperfusion was greater, the RPP during reperfusion was higher, and the UF recovery rate was lower in diabetic than in non-diabetic kidneys. 2)The RPP was increased by NE 10-7 M, which was higher in the diabetic than non-diabetiic kidneys; however, the UF recovery rate remained uninfluenced.3)Underperfusion and reperfusion injuries were not influenced by Glyb 10-6 M. 4)The influence of Glyb onunderperfusion and reperfusion injuries with NE was not seen in the diabetic kidneys. On the other hand, RPP during reperfusion increased in the non-diabetic kidneys. These results show diabetic kidneys to be more susceptible than non-diabetic kidneys to underperfusion and reperfusion injuries, being consistent with the previous studies on diabetic hearts. However, it was revealed that NE 10-7 M and Glyb 10-6 M did not affect the UF decrease due to these injuries. It was suggested that the RPP raised by the renal vascular smooth muscle constricted by NE and Glyb does not seem to influence the change in the UF caused by underperfusion and reperfusion injuries. Protection against underperfusion injuries by the KATP channel opening in diabetic kidneys proved to be unlikely.
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