联合肝脏离断和门静脉结扎术后大鼠肝再生的实验研究

Experimental study on portal vein ligation combined with in situ splitting on liver regeneration in rats

目的：探讨联合肝脏离断和门静脉结扎术对大鼠肝再生的影响。方法75只健康雄性SD大鼠随机分为假手术组（ S组）、单纯门静脉结扎组（ PVL组）和联合肝脏离断和门静脉结扎组（ ALPPS组）。分别于术后1、3、7、10、14天检测各组右中叶肝再生率、血清丙氨酸转氨酶（ ALT）、天冬氨酸转氨酶（AST）含量，IL-6、HGF和VEGF表达水平，肝组织IL-6、HGF、TNF-α、TGF-βmRNA表达及肝细胞增殖细胞核抗原（ PCNA）标记表达数量。结果与PVL组比较，ALPPS组术后第3、7、10、14天右中肝叶明显增生（P＜0．05），血清ALT和AST浓度术后第1天明显增高（P＜0．05），血清IL-6、HGF和VEGF表达水平于术后第1、3天明显增高，IL-6分别为（70.7±14.6） pg／ml、（134.2±31.4） pg／ml， HGF分别为（0.70±0.04）ng／ml、（0.74±0.02）ng／ml，VEGF分别为（82.1±12．6）pg／ml、（103．5±14．7）pg／ml（P＜0．05）。肝组织炎症因子mRNA表达水平及PCNA阳性表达数于术后第1、3天均明显增高（ P＜0.05）。 PVL和ALPPS两组术后各指标均高于S组（ P＜0.05）。结论联合肝脏离断和门静脉结扎术可显著促进肝再生。其再生机制可能与肝实质离断造成的肝脏炎症反应、应激反应以及促使某些细胞因子表达增高有关，尤其是IL-6、HGF和TNF-α等。

Objective To investigate the effect of portal vein ligation combined with in situ splitting on liver regeneration in rats .Methods Seventy-five healthy male Sprague-Dawley rats were selected and randomly assigned into sham operation group （ S） , portal vein ligation group （ PVL） and portal vein ligation combined with in situ splitting group （ ALPPS） .On 1 d, 3 d, 7 d, 10 d, 14 d after operation , the hepatic regeneration rate （ HRR） of right median lobe was calculated , the serum alanine aminotransferase （ ALT） , aspartate aminotransferase （AST）, IL-6, HGF, VEGF were detected.mRNA of IL-6, HGF, TNF-α, TGF-βwas assayed by real-time PCR, and the hepatic proliferating cell nuclear antigen （ PCNA） labeling index was evaluated by immunohistochemistry .Results Comparing with PVL group , the HRR of the right median lobe obviously increased on day 3, 7, 10 and 14 in ALPPS group （P〈0.05）, and ALT and AST level were increased on 1 d （P〈0.05）.On day 1 and 3, the content of serum IL-6, HGF and VEGF were all in-creased in ALPPS group [（70.7 ±14.6） pg/ml vs.（134.2 ±31.4） pg/ml; （0.70 ±0.04） ng/ml vs. （0.74 ±0.02） ng/ml;（82.1 ±12.6） pg/ml vs.（103.5 ±14.7） pg/ml], respectively （P〈0.05）.The mRNA expression of IL-6, HGF, TNF-α, TGF-βand the PCNA labeling index were also increased in ALPPS group in comparison with those in PVL group on day 1 and 3 （P〈0.05）.All the indexes in the two groups were all higher than those in the group S （ P〈0 .05 ） .Conclusions Portal vein ligation combined with in situ splitting could significantly enhance liver regeneration .The possible mechanisms were related to the inflammation reaction and stress response caused by in situ splitting and up-regulation of cytokines in the regenerating lobe after portal vein ligation combined with in situ splitting , especially IL-6, HGF and TNF-α.