Augmenter of Liver Regeneration Attenuates Tubular Cell Apoptosis in Acute Kidney Injury in Rats: The Possible Mechanisms
Augmenter of Liver Regeneration Attenuates Tubular Cell Apoptosis in Acute Kidney Injury in Rats: The Possible Mechanisms
复制标题
肝脏再生增强剂减轻大鼠急性肾损伤中管状细胞凋亡：可能的机制
DOI：
10.3109/0886022x.2012.664470
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发表时间：
2012-01-01
期刊：
影响因子：
3
通讯作者：
Guo, Hui
中科院分区：
文献类型：
--
作者：
Liao, Xiao-hui;Chen, Guo-tao;Guo, Hui
肝再生增强因子（Augmenter of Liver Regeneration，ALR）在大鼠肾缺血再灌注损伤（I/R）后表达增加，在体内和体外均能促进肾小管细胞再生。本研究旨在探讨ALR对肾I/R损伤后肾小管细胞凋亡的影响及其可能的机制。大鼠双侧肾缺血60分钟，然后再灌注给予载体或重组人ALR（rhALR）。通过测定血清生化指标和组织学分级评价肾功能损害和组织学损伤。采用末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记法（TUNEL）检测细胞凋亡。使用比色蛋白酶测定法测量胱天蛋白酶-3活性。免疫印迹法检测Bcl-2、Bax Fas、磷酸化Akt（p-Akt）和磷酸化p53（p-p53）的表达。与溶剂处理的大鼠相比，rhALR给药可显著减轻肾功能不全和组织学损伤。rhALR可降低肾小管上皮细胞凋亡率，下调Bax和p-p53表达，上调Bcl-2和p-Akt表达，下调caspase-3活性。而rhALR对Fas蛋白表达无影响。这些结果表明rhALR对肾I/R损伤的保护作用与其抗肾小管细胞凋亡作用有关。RhALR通过增加Bcl-2与Bax的比例和降低caspase-3的活性来抑制细胞凋亡。Akt的激活和p53的失活参与了rhALR的抗凋亡过程。
Augmenter of liver regeneration (ALR), the expression of which increased in rat kidneys after renal ischemia/reperfusion (I/R) injury, enhances renal tubular cell regeneration in vivo and in vitro. We aimed to investigate the effects of ALR on apoptosis of renal tubular cells after renal I/R injury in vivo and consider the possible mechanisms. Rats that were subjected to bilateral renal ischemia for 60 min followed by reperfusion were administered with either vehicle or recombinant human ALR (rhALR). Renal dysfunction and histologic injury were assessed by the measurement of serum biochemical markers and histological grading. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL). Caspase-3 activity was measured using a colorimetric protease assay. Expression of Bcl-2, Bax Fas, phosphorylated-Akt (p-Akt), and phosphorylated-p53 (p-p53) was determined by western blotting. Compared with vehicle-treated rats, renal dysfunction and histologic injury were significantly attenuated by administration of rhALR. The number of TUNEL-positive tubular cells and caspase-3 activity were decreased, Bcl-2 and p-Akt expression was up-regulated, and Bax and p-p53 expression was down-regulated by administration of rhALR. However, administration of rhALR had no effect on Fas protein expression. These results indicate that the protective effect of rhALR on renal I/R injury is associated with its anti-apoptotic action in renal tubular cells. RhALR inhibits apoptosis by increasing the ratio of Bcl-2 to Bax and by decreasing the activity of caspase-3. The activation of Akt and inactivation of p53 are involved in the rhALR anti-apoptosis process.