Li Deming, Li Jun, Wang Gaiping, Qin Yanli, Niu Zhipeng, Li Ziwei, Xu Cunshuan
Key Laboratory for Cell Differentiation Regulation, Xinxiang, China.
College of Life Science, Henan Normal University, Xinxiang, China.
Cell J. 2017 Jul-Sep;19(2):218-230. doi: 10.22074/cellj.2016.4878. Epub 2017 Feb 22.
Patients over 60 years of age have higher mortality and morbidity after major liver resections. Nitric oxide (NO) derived from the catalytic activity of Nos2 plays a beneficial role in liver regeneration (LR) after partial hepatectomy (PH). In this experiment, we evaluated the effect of knockout (KO) on LR in aged mice after PH.
In this experimental study, 52 two-year-old KO and 46 the same age wild-type (WT) C57BL/6J mice were subjected to 2/3 PH. Liver tissues were collected at 11 time points after PH. Mice survival ratio and liver coefficient (liver-weight/ body-weight) was calculated. Transcript and protein levels were estimated by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively.
The aged KO mice had lower survival ratio (P=0.039) and liver coefficient (P=0.002) at the termination phase. transcript level was obviously increased after PH in WT mice and undetected in the KO mice. During LR, the expression at the transcript level of and and protein expression level of proliferation marker Ki67 and proliferation-associated transcription factors JNK1, NF-kB and STAT3 were decreased or delayed. The expression of pro-apoptotic proteins, CASPASE3, CASPASE9 and BAX, was increased in the KO mice.
Decreased survival ratio and impaired LR in aged KO mice is probably due to decreased liver cell proliferation and increased liver cell apoptosis.
60岁以上患者在接受大肝切除术后具有更高的死亡率和发病率。由Nos2催化活性产生的一氧化氮（NO）在部分肝切除（PH）后的肝再生（LR）中发挥有益作用。在本实验中，我们评估了基因敲除（KO）对老年小鼠PH后LR的影响。
在本实验研究中，52只两岁的KO和46只同龄野生型（WT）C57BL/6J小鼠接受了2/3 PH手术。在PH后的11个时间点采集肝组织。计算小鼠存活率和肝系数（肝重/体重）。分别通过逆转录定量聚合酶链反应（RT-qPCR）和蛋白质印迹法评估转录本和蛋白质水平。
在终末期，老年KO小鼠的存活率（P=0.039）和肝系数（P=0.002）较低。WT小鼠在PH后转录本水平明显升高，而在KO小鼠中未检测到。在LR期间， 、 的转录本水平表达以及增殖标志物Ki67和增殖相关转录因子JNK1、NF-kB和STAT3的蛋白质表达水平降低或延迟。KO小鼠中促凋亡蛋白CASPASE3、CASPASE9和BAX的表达增加。
老年KO小鼠存活率降低和LR受损可能是由于肝细胞增殖减少和肝细胞凋亡增加所致。
