Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Nephrol Dial Transplant. 2010 Sep;25(9):2921-9. doi: 10.1093/ndt/gfq151. Epub 2010 Mar 23.
Augmenter of liver regeneration (ALR), which was identified originally for its crucial role in promoting hepatocyte proliferation, is expressed in both the liver and kidney. Protective effects of ALR have been demonstrated in experimental models of acute liver failure. In the present study, we investigated the effect of ALR on renal ischaemia/reperfusion (I/R) injury and the possible mechanisms of its action.
Male Sprague-Dawley rats were subjected to renal ischaemia for 60 min and then administered with either saline or recombinant human ALR (rhALR). A sham-operated group served as control. The expression of ALR in the sham-operated and acute kidney injury (AKI) groups was detected by immunohistochemistry and western blotting. Renal dysfunction and injury were assessed by measurement of serum biochemical markers and histological grading. Expression of proliferating cell nuclear antigen (PCNA) was determined by immunohistochemistry.
Renal ALR expression increased significantly in rats with ischaemic AKI compared with the sham-operated rats. Serum biochemical parameters showed that renal dysfunction was improved by administration of rhALR. Histological analysis revealed that treatment with rhALR also reduced the extent of kidney injury. Intraperitoneal injection of rhALR enhanced the proliferation of renal tubular cells. Conclusions. Administration of rhALR effectively reduces tubular injury and ameliorates the impairment of renal function. The protective effect of rhALR is associated with enhancement of renal tubular cell regeneration.
最初被鉴定为促进肝细胞增殖的关键因子的肝再生增强因子 (ALR) 在肝脏和肾脏中均有表达。ALR 在急性肝衰竭的实验模型中已显示出保护作用。在本研究中,我们研究了 ALR 对肾缺血/再灌注 (I/R) 损伤的影响及其作用机制。
雄性 Sprague-Dawley 大鼠进行 60 分钟的肾缺血,然后给予生理盐水或重组人 ALR (rhALR)。假手术组作为对照。通过免疫组织化学和 Western blot 检测 sham 操作组和急性肾损伤 (AKI) 组中 ALR 的表达。通过测量血清生化标志物和组织学分级来评估肾功能和损伤。通过免疫组织化学检测增殖细胞核抗原 (PCNA) 的表达。
与 sham 操作组相比,缺血性 AKI 大鼠的肾 ALR 表达明显增加。血清生化参数显示,rhALR 的给药改善了肾功能障碍。组织学分析表明,rhALR 的治疗还减轻了肾脏损伤的程度。腹腔内注射 rhALR 增强了肾小管细胞的增殖。结论。rhALR 的给药可有效减轻肾小管损伤,改善肾功能障碍。rhALR 的保护作用与增强肾小管细胞再生有关。