关键词: 肝部分切除术, N-乙酰基转移酶10, 肝再生, 增殖细胞核抗原, 小鼠

Abstract: Objective The liver is the only visceral organ with significant self-regeneration capability, which is fundamental to the success of liver surgical procedures. This study aimed to investigate the role of N-acetyltransferase 10 (NAT10) in liver regeneration process. Methods A hepatocyte-specific NAT10 conditional knockout (CKO) mouse model was established by using the Cre-Lox P system, and partial hepatectomy (PH) was performed both in Twenty wild-type (WT) C57BL/6J mice (Flox) and in CKO mice. By 0 h,24 h,48 h and 72 h after PH, NAT10 and proliferating cell nuclear antigen (PCNA) RNA and protein expression were detected by qPCR and Western bloting. Liver index was also calculated. Results In WT mice, hepatic NAT10 mRNA and protein expression levels at 24 hours after PH were (1.4±0.1) and (3.6±0.2), respectively, both significantly higher than [(1.0±0.1) and (0.9±0.3), P<0.05] at 0 hour, but significantly lower than [(1.9±0.1) and (10.0±1.6), P<0.05] at 48 hour; by 72 hours, hepatic NAT10 mRNA and protein levels were (0.9±0.1) and (1.0±0.4), also significantly lower than [(1.9±0.1) and (10.0±1.6), respectively, P<0.05] by 48 hour; a CKO mouse model was successfully established and the knockout efficiency was confirmed; NAT10 mRNA level in the CKO group was (0.2±0.1), significantly lower than [(1.0±0.1, P<0.05), and NAT10 protein level was (0.1±0.0), also significantly lower than [(1.0±0.1, P<0.05) in the Flox group; at 0 hours after PH, the liver index in the Flox and CKO groups were (5.0±0.5)% and (5.5±0.3)%, showing no significantly different (P>0.05); at 24 h, 48 h and 72 h after PH, the liver index in the CKO group were (2.7±0.1)%, (2.7±0.0)% and (3.1±0.0)%, all significantly lower than[(3.6±0.1)%, (3.9±0.1)% and (4.6±0.1)%, respectively, P<0.05] in the Flox group; additionally, the PCNA mRNA levels in the CKO group were (0.6±0.0), (0.3±0.0) and (0.5±0.0), all significantly lower than [(1.1±0.1), (1.0±0.1) and (1.0±0.2), respectively, P<0.05] in the Flox group; the PCNA protein levels in the CKO group were (0.3±0.1), (0.7±0.0) and (0.7±0.0), all significantly lower than [(1.0±0.1), (1.0±0.1) and (1.0±0.1), respectively, P<0.05] in the Flox group. Conclusion NAT10 promotes liver regeneration in a mouse model of PH. These findings suggest that NAT10 might be a potential biomarker for predicting prognosis after liver resection or liver transplantation.

Key words: Partial hepatectomy, N-acetyltransferase 10, Liver regeneration, Proliferating cell nuclear antigen, Mice