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运动预处理可减少 Hsp70.1 敲除小鼠的急性缺血性肾损伤。

Exercise preconditioning reduces acute ischemic renal injury in Hsp70.1 knockout mouse.

机构信息

Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul, Korea.

出版信息

Histol Histopathol. 2013 Sep;28(9):1223-33. doi: 10.14670/HH-28.1223. Epub 2013 Jun 19.

DOI:10.14670/HH-28.1223
PMID:23780557
Abstract

BACKGROUND/AIMS: Heat shock protein 70 (Hsp70) is an anti-apoptotic protein that has a protective effect in renal ischemic injury. Exercise up-regulates Hsp family proteins (Hsps), antioxidants and anti-apoptotic proteins. We hypothesized that exercise as preconditioning could attenuate acute renal dysfunction and apoptosis resulting from renal ischemic injury under the Hsp70 deficient circumstance and could contribute to the prevention of renal injury induced by ischemia.

METHOD

To investigate the effect of exercise preconditioning on protecting the kidney from ischemia in Hsp70 deficiency, we measured apoptosis-related factors and Hsps. Hsp70.1 KO and wild-type mice were divided into sham control (Sham), exercise preconditioning (Ex), renal ischemia-after-exercise (Ex+IR), and ischemia (IR) groups. Where appropriate a treadmill exercise was performed at 20 m/min, 60 min per day on a 0% gradient for 7 days, and renal ischemia was induced by clamping the renal pedicle for 25 min. To characterize the effects of exercise on oxidative stress- and apoptosis-related factors, and Hsp27 and 70 expressions, we performed immunohistochemistry, western blotting and TUNEL assay, and also measured level of serum creatinine.

RESULTS

Serum creatinine concentration and 4-HNE expression were raised in the IR group, as were caspases 3, 7 and 9, while Cu- and Mn-SOD levels were reduced, as were those of anti-apoptotic proteins Bcl-XL, Bcl-2 and Hsp27. All these effects were largely reversed by the exercise preconditioning, as was the decrease in apoptotic cells observed after exercise preconditioning.

CONCLUSION

Exercise preconditioning has a beneficial effect in inhibiting oxidative stress and apoptotic cell death in the kidney resulting from ischemic injury even under Hsp70 deficiency.

摘要

背景/目的:热休克蛋白 70(Hsp70)是一种抗细胞凋亡蛋白,在肾缺血性损伤中具有保护作用。运动可上调热休克蛋白家族蛋白(Hsps)、抗氧化剂和抗细胞凋亡蛋白。我们假设,运动预处理可以减弱 Hsp70 缺乏情况下肾缺血引起的急性肾功能障碍和细胞凋亡,并有助于预防缺血引起的肾损伤。

方法

为了研究运动预处理对 Hsp70 缺乏情况下保护肾脏免受缺血的影响,我们测量了与细胞凋亡相关的因素和 Hsps。将 Hsp70.1 KO 和野生型小鼠分为假手术对照(Sham)、运动预处理(Ex)、运动后肾缺血(Ex+IR)和缺血(IR)组。在适当的时候,在 0%坡度上以 20 m/min、每天 60 min 的速度进行跑步机运动 7 天,并夹闭肾蒂 25 min 诱导肾缺血。为了研究运动对氧化应激和细胞凋亡相关因子以及 Hsp27 和 70 表达的影响,我们进行了免疫组织化学、Western blot 和 TUNEL 检测,还测量了血清肌酐水平。

结果

血清肌酐浓度和 4-HNE 表达在 IR 组升高,caspase 3、7 和 9 也升高,而 Cu 和 Mn-SOD 水平降低,抗凋亡蛋白 Bcl-XL、Bcl-2 和 Hsp27 也是如此。运动预处理在很大程度上逆转了这些效应,运动预处理后观察到的凋亡细胞减少也是如此。

结论

运动预处理对 Hsp70 缺乏情况下缺血性损伤引起的肾脏氧化应激和凋亡细胞死亡具有有益作用。

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