关键词: 肝切除, 代谢组, 苯丙氨酸合成, 初级胆汁酸合成, 烟酰胺代谢

Abstract:

This study aimed to analyze the serum metabolome changes following laparoscopic hepatic lobectomy in Beagle dogs and explore the underlying mechanisms of these metabolic alterations. Eight healthy Beagle dogs of similar weight were selected to establish a liver lobectomy model. Serum samples were collected preoperatively, and at 7 and 14 days post-surgery. Ultra high performance liquid tandem chromatography quadrupole time of flight mass spectrometry(UHPLC-QTOFMS) was employed to detect changes in serum metabolites during the perioperative period. The results demonstrated that: Principal component analysis (PCA) revealed a clear separation between the 7-day post-surgery group and the preoperative group, indicating significant differences in metabolites between these time points. In contrast, the overlap between the 14-day post-surgery group and the preoperative group suggested a gradual return to preoperative status by day 14. The orthogonal partial least squares discriminant analysis (OPLS-DA) score plot and model validation indicated that the constructed model possessed good explanatory and predictive capabilities without overfitting. Differential metabolites were identified using the variable importance in projection (VIP) score>1 for the first principal component of the OPLS-DA model, with a significance level of P<0.05 by t test. Compared to the preoperative period, 35 differential metabolites were detected at 7 days post-surgery, with 13 down-regulated and 22 up-regulated. Notably, L-phenylalanine was involved in phenylalanine, tyrosine, and tryptophan biosynthesis, as well as phenylalanine metabolism and aminoacyl-tRNA biosynthesis, while 3α, 7α-dihydroxy-5b-cholestane was implicated in primary bile acid biosynthesis. At 14 days post-surgery, 42 differential metabolites were identified, with 19 down-regulated and 23 up-regulated, including 1-methylnicotinamide and nicotinamide, which were involved in niacin and nicotinamide metabolism. Fewer metabolites showed changes at 14 days compared to 7 days after surgery. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway enrichment results showed that the differential metabolites were significantly enriched in the metabolic pathways of phenylalanine, tyrosine, and tryptophan biosynthesis, and primary bile acid biosynthesis at 7 d postoperatively as compared to preoperatively; Laparoscopic hepatic lobectomy resulted in significant alterations in several metabolites. The biosynthesis of phenylalanine, tyrosine, tryptophan, and primary bile acids played important roles in the metabolic mechanisms underlying liver injury, while the metabolic pathway of nicotinate and nicotinamide contributed to the liver recovery process.

Key words: hepatectomy, metabolome, synthesis of phenylalanine, primary bile acid synthesis, nicotinamide metabolism