Past Issue

Volume 19, Number 2, Jul-Sep (Summer) 2017, Serial Number: 74 Pages: 218-230

Delayed Liver Regeneration after Partial Hepatectomy in Aged Nos2 Knockout Mice


Deming Li, Ph.D, 1, 2, Jun Li, B.Sc, 1, 2, Gaiping Wang, Ph.D, 1, 2, Yanli Qin, B.Sc, 1, 2, Zhipeng Niu, B.Sc, 1, 2, Ziwei Li, B.Sc, 1, 2, Cunshuan Xu, Ph.D, 1, 2, *,
Key Laboratory for Cell Differentiation Regulation, Xinxiang, China
College of Life Science, Henan Normal University, Xinxiang, China
*Corresponding Address: College of Life Science Henan Normal University 46# East of Construction Road Xinxiang 453007 Henan PR China Email:cellkeylab@126.com

Abstract

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.