Delayed Liver Regeneration after Partial Hepatectomy in Aged Nos2 Knockout Mice

• Published in: Cell journal (Yakhteh) 2017-07, Vol.19 (2), p.218-230
• Main Authors: Li, Deming, Li, Jun, Wang, Gaiping, Qin, Yanli, Niu, Zhipeng, Li, Ziwei, Xu, Cunshuan
• Format: Article
• Language: English
• Subjects: Actin; Aged; Aging; Aging (artificial); Anesthesia; Angiogenesis; Animal welfare; Animals; Antibodies; Apoptosis; Blood pressure; Body mass; Body weight; Bone marrow; Breast cancer; Calcium; Cell growth; Chemical synthesis; Deoxyribonucleic acid; Differentiation; DNA; Gene expression; Gene regulation; Gray scale; Hemorrhage; Hepatectomy; Hepatology; Hyperplasia; Hypertension; Infants; Inflammation; Inhibition; Interleukin 6; Ischemia; Isoforms; JNK protein; Kinases; Laboratory animals; Life span; Light effects; Liver; Liver diseases; Liver Regeneration; Lobes; Mathematical analysis; Mathematical models; Membranes; Mice; Milk; Mitosis; Morbidity; Nitric oxide; Older people; Organs; pH effects; Polymerase chain reaction; Proliferation; Proteins; Recovery of function; Ribonucleic acid; RNA; Robotics; Rodents; Senescence; Sensitizing; Studies; Survival; Temperature effects; Transcription factors; Tumor necrosis factor-TNF; Ventilation
• ISSN: 2228-5806; 2228-5814
• DOI: 10.22074/cellj.2017.4878

Objective 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 Nos2 knockout (KO) on LR in aged mice after PH. Materials and Methods In this experimental study, 52 two-year-old Nos2 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. Results The aged Nos2 KO mice had lower survival ratio (P=0.039) and liver coefficient (P=0.002) at the termination phase. Nos2 transcript level was obviously increased after PH in WT mice and undetected in the Nos2 KO mice. During LR, the expression at the transcript level of Cyclin D1, Cyclin A2 and Cyclin B1 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 Nos2 KO mice. Conclusion Decreased survival ratio and impaired LR in aged Nos2 KO mice is probably due to decreased liver cell proliferation and increased liver cell apoptosis.