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 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

Human insulin inhibits apoptosis and promotes proliferation of rat liver cell line BRL-3 A / 基础医学与临床

Objective_To study the effect of human insulin on cell cycle progression and apoptosis of rat liver cell line BRL-3A in vitro.Methods_MTT method was used to observe the effect of insulin on cell activity, and flow cytometry was used to detect cell apoptosis and cell cycle.qRT-PCR was used to evaluate the expression of related genes.Results_Human insulin induced the proliferation of BRL-3A cells in a dose-dependent manner ( P<0.05 or P<0.01);After 3 days treated by human insulin (500 nmol/L), the proportion of cells in G0/G1 phases re-markably decreased (P<0.05).Moreover, pro-apoptotic BAX was down-regulated (P<0.05), while cell prolif-eration-related gene CCNA2 was up-regulated (P<0.05).Conclusions_Human insulin may inhibit the apoptosis of BRL-3 A cell line and induce proliferation due to the down-regulated expression of BAX and up-regulated expres-sion of CCNA2 .