Davies S J, Reichardt-Pascal S Y, Vaughan D, Russell G I
Renal Laboratory, School of Post-Graduate Medicine, University of Keele, Staffs, UK.
Exp Nephrol. 1995 Nov-Dec;3(6):348-54.
In the kidney, ischaemia-reperfusion results in both hypoxic and oxidant cellular injury which is most marked in the tubules of cortex and outer medulla. These contrasting conditions may have opposite effects on the expression of enzymes that reduce or repair oxidant damage. To investigate this, the activities of CuZn and Mn superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) were measured after 4 h and 3, 6, and 10 days of reperfusion following sham surgery or 45- or 90-min left renal artery occlusion. The right kidney served as internal control. Sham surgery had no effect on Mn SOD or GPx, but caused small (p < 0.05) reductions in CuZn SOD and GST activities. Forty-five minutes of ischaemia had no net effect on Mn SOD, increased GPx activity (maximum at 6 days, p < 0.01), and reduced CuZn SOD (nadir 3 days, p < 0.02) and GST (nadir 6 days, p < 0.02) activities. Ninety minutes of ischaemia again had no net effect on Mn SOD, prevented the induction of GPx, and further suppressed the activities of CuZn SOD and GST. The activity of the non-anti-oxidant enzyme lactate dehydrogenase was equal in left and right kidneys after 45 min of ischaemia, but different (p < 0.01) 10 days following 90-min injury, due to a combination of reduced activity in the ischaemic kidney and an increase of activity in the internal control. The immediate effect of ischaemia-reperfusion injury on the kidney is to reduce the activity of intracellular anti-oxidant enzymes in proportion to the severity of the ischaemic insult. Recovery or net induction of enzyme activity paralleled tubular regeneration. Protection resulting in acquired resistance to a second ischaemic event is unlikely to be due to induction of anti-oxidant enzymes if it occurs within 6 days.
在肾脏中，缺血再灌注会导致缺氧和氧化性细胞损伤，这种损伤在皮质和外髓质的肾小管中最为明显。这些截然不同的情况可能对减少或修复氧化性损伤的酶的表达产生相反的影响。为了对此进行研究，在假手术或左肾动脉闭塞45分钟或90分钟后再灌注4小时、3天、6天和10天后，测量了铜锌超氧化物歧化酶（SOD）、锰超氧化物歧化酶、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽S-转移酶（GST）的活性。右肾作为内部对照。假手术对锰超氧化物歧化酶或谷胱甘肽过氧化物酶没有影响，但导致铜锌超氧化物歧化酶和谷胱甘肽S-转移酶活性小幅降低（p<0.05）。45分钟的缺血对锰超氧化物歧化酶没有净影响，增加了谷胱甘肽过氧化物酶活性（在第6天达到最大值，p<0.01），并降低了铜锌超氧化物歧化酶（第3天最低，p<0.02）和谷胱甘肽S-转移酶（第6天最低，p<0.02）活性。90分钟的缺血再次对锰超氧化物歧化酶没有净影响，阻止了谷胱甘肽过氧化物酶的诱导，并进一步抑制了铜锌超氧化物歧化酶和谷胱甘肽S-转移酶的活性。缺血45分钟后，非抗氧化酶乳酸脱氢酶的活性在左肾和右肾中相等，但在90分钟损伤后10天有所不同（p<0.01），这是由于缺血肾中活性降低和内部对照中活性增加共同导致的。缺血再灌注损伤对肾脏的直接影响是使细胞内抗氧化酶的活性与缺血损伤的严重程度成比例降低。酶活性的恢复或净诱导与肾小管再生平行。如果在6天内发生，导致对第二次缺血事件获得性抗性的保护不太可能是由于抗氧化酶的诱导。
