Effects of interfering liver regeneration pathways on rat survival after extensive hepatectomy

Objective To investigate the effects of inhibiting cyclooxygenase-2 (COX-2) or/and Kupffer cells on rat survival and liver regeneration after extensive hepatectomy.Methods Healthy SD rats were treated with NS-398 or/and gadolinium chloride (GdCl3) 1 h after undergoing extensive hepatectomy.Rat survival rate,remnant liver growth,serum ALT and proliferating cell nuclear antigen (PCNA) immunoreactivity in the liver were detected on the postoperative day 2 and 7.Results The maximum size was 85％ for safe live resection in SD rats and the survival rate was decreased to 30％ in rats treated with GdCl3 (GdCl3 group) and GdCl3 combined with NS-398 (GdCl3/NS-398 group).On the day 2 after surgery and treatment,remnant liver regeneration ratio in GdCl3 group was (1.23 ± 0.21)％,significantly higher than that in vehicle group [(0.95 ± 0.08) ％,P ＜ 0.05].Immunohistochemical analysis for PCNA revealed that hepatocyte proliferation was enhanced by GdCl3,but it was retarded by NS-398.In addition,serum ALT level was higher in GdCl3 and GdCl3/NS-398 groups than in the other two groups.Conclusion Inhibition of COX-2 suppressed early liver regeneration without affecting rat survival after extensive hepatectomy,whereas Kupffer cell depletion resulted in toxic effect on the remnant liver and increased postoperative mortality,though it enhanced early liver regenerative response. Key words: Hepatectomy;  Liver regeneration ;  Cyclooxygenase-2