ラット虚血腎モデルにおけるCsA-induced Nephropathy : 腎および全身循環動態と腎ミクロゾームチトクロームP-450の変動ならびにCa拮抗剤の影響

Abstract

片側腎摘ラットの腎動脈を20分間閉塞して虚血腎モデルを作製し, CsA, verapamil (V)併用時の全身循環動態, 肝・腎ミクロゾームP-450の変動を検討した.動物は対照群(C群), CsA群, CsA+V群, Is群, IS+CsA群, Is+CsA+V群の6群に分けた.1) CsAは各群の血中BUN, 血清クレアチニン(sCr)を有意に増加せしめ, 腎イヌリンクリアランス(Cin)を有意に減少せしめた.Is群に比べてCsAは心拍出量を有意に減少せしめ, 特に血中BUN, sCrが有意に減少していたIs+CsA群の腎血流量は減少していた.CsA+V群のCinもまたIs群より有意に減少していた.Is+CsA+V群のCinと腎血流量はIs+CsA群より有意に上昇していた.2)腎ミクロゾームチトクロームP-450比含量, ラウリン酸およびPGAω水酸化酵素活性の増加はIs+CsA群で認められた.3)正常腎におけるCsA-induced Nephropathyの進展はVで抑制できなかったが, 虚血腎では明らかにその進展がVによって抑制された

We have examined the effect of verapamil on CsA-induced nephropathy by measurement of systemic hemodynamics including each organ blood flow using the microsphere method in ischemic kidney model of hemi-nephrectomized Wistar rats. Hepatic and renal microsomal cytochrome P-450 contents and their enzyme activities were measured to study the correlation between CsA-induced nephropathy and induction of hepatic and renal microsomal cytochrome P-450. All rats were hemi-nephrectomized (l-nephrectomy) and were classified into the following 6 groups: 1) control groups, 2) CsA at a dose of 40 mg/kg per day orally for 7 days (CsA group), 3) Oral administration of verapamil for 7 days in the CsA group (CsA + V group), 4) 20 min clamping of the remaining right kidney pedicle (Ischemic, Is group), 5) CsA was administered in the Is group (Is + CsA group), 6) Addition of verapamil to CsA in the Is + CsA group (Is + CsA + V group). Verapamil was given in the drinking water and the average dose calculated from the amount of drinking was 4.7 +/- 1.0 mg/kg per day and 5.2 +/- 0.7 mg/kg per day for the CsA + V group and the Is + CsA + V group, respectively. CsA caused significant increases in BUN and serum creatinine (sCr) with a significant decreases in renal inulin clearance (CIn) in all groups. When compared with the Is group, CsA caused significant decreases in cardiac output and all organ blood flow especially in renal blood flow with significant increases in BUN and sCr in the Is + CsA group.2+ degree of nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)