Delayed Liver Regeneration after Partial Hepatectomy in Aged Nos2 Knockout Mice

Area of Science:

• Hepatology and regenerative medicine
• Molecular biology and genetics
• Surgical research

Background:

• Major liver resections in patients over 60 are associated with increased mortality and morbidity.
• Nitric oxide (NO), produced by Nos2, is crucial for liver regeneration (LR) following partial hepatectomy (PH).

Purpose of the Study:

• To investigate the impact of Nos2 knockout (KO) on liver regeneration in aged mice post-PH.
• To assess the role of Nos2 in maintaining liver function and survival during liver regeneration in elderly individuals.

Main Methods:

• Aged Nos2 knockout (KO) and wild-type (WT) mice (C57BL/6J) underwent 2/3 partial hepatectomy (PH).
• Liver tissues were analyzed at 11 time points post-PH.
• Survival rates, liver coefficients, and gene/protein expression (RT-qPCR, Western blot) were evaluated.

Main Results:

• Aged Nos2 KO mice exhibited significantly lower survival ratios and liver coefficients compared to WT mice.
• Nos2 transcript levels increased post-PH in WT mice but were absent in KO mice.
• Key cell cycle regulators (Cyclin D1, A2, B1) and proliferation markers (Ki67, JNK1, NF-kB, STAT3) showed decreased or delayed expression in KO mice.
• Pro-apoptotic proteins (CASPASE3, CASPASE9, BAX) were upregulated in aged Nos2 KO mice.

Conclusions:

• Nos2 deficiency impairs liver regeneration in aged mice, leading to reduced survival.
• The observed impairment is attributed to diminished hepatocyte proliferation and heightened apoptosis.
• Targeting Nos2 pathways may be a therapeutic strategy to improve outcomes after liver surgery in the elderly.