Delayed Liver Regeneration after Partial Hepatectomy in Aged Nos2 Knockout Mice.

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 knockout (KO) on LR in aged mice after PH.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

Decreased survival ratio and impaired LR in aged KO mice is probably due to decreased liver cell proliferation and increased liver cell apoptosis.