Pathogenesis of ischemia reperfusion injury of the kidney after transient renal arterial clamping in rats.
Renal function can be severely impaired through injuries sustained after both short and prolonged periods of complete ischemia. The magnitude of renal dysfunction resulting from these conditions and their reversibility depend on the duration of anoxia. In this study, we used a Sprague-Dawley rat model (5 to 7 rats in each group) to study the pathogenesis of short-term ischemia (30, 60, and 120 min)/reperfusion (2, 4, 24 h, 1 wk, and 3 wk) injury of the kidney under warm (room temperature) or cold (4 degrees C) conditions. Ischemia was induced by clamping the renal artery. Changes in kidney weight, histopathology, concentrations of serum thromboxane and leukotriene, and tissue malonyldialdehyde (MDA) concentration, numbers of apoptotic bodies, and p53 expression in the kidney were compared with those of sham-operated rats. The results showed that the immediate increase in kidney weight due to inflammatory swelling was associated with simultaneous elevation of serum thromboxane and leukotriene levels. The changes in mediator levels were closely related to the duration of ischemia and temperature. Histologic structures were preserved better when renal artery clamping was done at 4 degrees C. MDA peroxidation products from the ischemic tissue prominently increased 1 week following ischemia; this paralleled a secondary increase in leukotriene levels. Flow cytometric detection of p53 oncoprotein showed a marked increase at 1 week following ischemia, which was accompanied by the development of apoptotic bodies in ischemic tissues. These changes were also closely related to the ischemic time and temperature during ischemia. This animal model may be useful for future studies of the prevention of ischemia/reperfusion injury of the kidney and for selection of effective antioxidants.
Yu
D S
DS
Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Char
D L
DL
Chang
S Y
SY
Ma
C P
CP
D000818:Animals; D017209:Apoptosis; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D007975:Leukotriene B4 / Q000097:blood; D015227:Lipid Peroxidation; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012078:Renal Artery Obstruction / Q000150:complications*; D015427:Reperfusion Injury / Q000209:etiology*; D013929:Thromboxane B2 / Q000097:blood
D007975:Leukotriene B4; D013929:Thromboxane B2