Lin K C, Krieg R J, Saborio P, Chan J C
Department of Pediatrics, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, Virginia, 23298, USA.
Mol Genet Metab. 1998 Dec;65(4):303-10. doi: 10.1006/mgme.1998.2770.
Our previous studies noted the oxidative stress of unilateral ureteral obstruction (UUO). Now, we seek to explore whether UUO affects the intrinsic cellular antioxidants and triggers heat shock protein (HSP-70) and whether these are still highly expressed after reversal of the UUO (R-UUO). In addition, we designed the experiment to determine whether this expression of HSP-70 is a localized or a generalized response. Male Sprague-Dawley rats (125-150 g) were randomly assigned to sham operation, left UUO, or R-UUO procedures at six rats per group. The sham, UUO, and R-UUO animals were studied 10 days after UUO or 7 days after R-UUO. A clear increase in the left (obstructed) kidney's malondialdehyde (MDA), a marker of lipid peroxidation, was observed: a significant 2.6-fold of sham during UUO and a 1.7-fold of sham in R-UUO. The contralateral (unobstructed) right kidney showed a significant rise in MDA during UUO, but during R-UUO the MDA had fallen back to sham values. It is possibly the result of a systemic effect from the free radicals produced by the oxidative stress of the UUO. The antioxidant enzyme, manganese superoxide dismutase (MnSOD) of the left, obstructed kidney showed a significant reduction in UUO compared to that of the sham. Upon reversal of UUO (R-UUO), MnSOD was lower than that of the sham. The left kidney's HSP-70 increased during UUO and was 3.7-fold that of sham (P < 0.05) but, during R-UUO, was not different from sham (P, ns). The contralateral (intact) right kidneys' HSP-70 showed no change between sham, UUO, and R-UUO states. We conclude that UUO gives rise to oxidative stress which is generalized in both the obstructed and the contralateral unobstructed kidney, as indicated by the elevation in kidney MDA content in both kidneys. The intrinsic cellular antioxidant enzyme, manganese superoxide dismutase, showed a significant and generalized reduction in both UUO and R-UUO. In contrast, the HSP-70 was markedly elevated only in the obstructed kidney and not in the R-UUO or in the contralateral kidney, suggesting that the elevation of HSP-70 is a specific and localized response to oxidative injury of UUO.
我们之前的研究注意到单侧输尿管梗阻（UUO）存在氧化应激。现在，我们试图探究UUO是否会影响细胞内源性抗氧化剂并触发热休克蛋白（HSP - 70），以及在UUO解除（R - UUO）后这些物质是否仍高表达。此外，我们设计实验来确定HSP - 70的这种表达是局部反应还是全身反应。将雄性Sprague - Dawley大鼠（125 - 150克）随机分为假手术组、左侧UUO组或R - UUO组，每组6只大鼠。在UUO术后10天或R - UUO术后7天对假手术组、UUO组和R - UUO组动物进行研究。观察到左侧（梗阻）肾脏中脂质过氧化标志物丙二醛（MDA）明显增加：UUO期间是假手术组的2.6倍，R - UUO期间是假手术组的1.7倍。对侧（未梗阻）右肾在UUO期间MDA显著升高，但在R - UUO期间MDA已回落至假手术组水平。这可能是UUO氧化应激产生的自由基引起全身效应的结果。左侧梗阻肾脏的抗氧化酶锰超氧化物歧化酶（MnSOD）与假手术组相比在UUO时显著降低。在UUO解除（R - UUO）后，MnSOD低于假手术组。左侧肾脏的HSP - 70在UUO期间增加，是假手术组的3.7倍（P < 0.05），但在R - UUO期间与假手术组无差异（P，无统计学意义）。对侧（完整）右肾的HSP - 70在假手术组、UUO组和R - UUO组之间无变化。我们得出结论，UUO会引发氧化应激，这在梗阻侧肾脏和对侧未梗阻肾脏中都是全身性的，这由双侧肾脏中MDA含量升高表明。细胞内源性抗氧化酶锰超氧化物歧化酶在UUO和R - UUO中均显著且全身性降低。相比之下，HSP - 70仅在梗阻侧肾脏中显著升高，在R - UUO或对侧肾脏中未升高，这表明HSP - 70的升高是对UUO氧化损伤的特异性局部反应。
