D-氨基半乳糖与脂多糖对小鼠肝脏损伤后再生修复的影响

Influences of D-galactosamine and lipopolysaccharide on liver tissue regeneration and repair in mice with partial hepatectomy

目的观察部分肝切除联合D-氨基半乳糖(D-GaIN)、脂多糖对肝损伤后再生修复的影响。方法 40只BALB/c雄性小鼠随机均分为2组。D-GaIN/脂多糖/肝脏部分切除组:腹腔注射D-GaIN(500 mg/kg),1 h后注射脂多糖(50μg/kg);肝脏部分切除组:生理盐水代替D-GaIN和脂多糖,同样方法注射;两组小鼠在第2次腹腔注射24 h后行肝脏1/3切除。观察两组小鼠术后肝脏体质量比值、肝再生率、肝细胞损伤、增殖与肝卵圆干细胞增生。结果肝脏部分切除组术后第9天肝大体结构基本恢复正常,肝再生率为(22.26±105.93)%,而D-GaIN/脂多糖/肝脏部分切除组第14天肝质量较术前仍偏小,肝再生率为(9.49±32.55)%,P<0.001。D-GaIN/脂多糖/肝脏部分切除组术后肝窦和中央静脉充血,库普弗细胞增多;肝脏部分切除组术后第7天有明显肝细胞增殖,D-GaIN/脂多糖/肝脏部分切除组肝细胞增殖甚少。D-GaIN/脂多糖/肝脏部分切除组肝脏术后第3天开始出现肝卵圆干细胞增生,从汇管区开始向肝小叶内延伸以修复损伤。结论 D-GaIN联合脂多糖可部分抑制肝部分切除后小鼠成熟肝细胞增殖,D-GaIN/脂多糖/肝部分切除可诱导肝卵圆干细胞增生。

Objective To observe the effect of D-galactosamine（D-GaIN） and lipopolysaccharide（LPS） on liver tissue regeneration and repair in mice following liver injury induced by partial hepatectomy.Methods A total of 40 male BALB/c mice were randomly assigned into 2 equal groups to receive intraperitoneal injections of D-GaIN（500 mg/kg） plus LPS（50 μg/kg,given 1 h later） or two doses of saline 24 h prior to 1/3 hepatectomy.The liver weight/body weight（LW/BW） ratio and liver regeneration rate were observed at different time points after partial hepatectomy.Liver cell injury was assessed using HE staining,hepatocyte proliferation evaluated with BrdU staining,and the oval cell proliferation observed with immunohistochemistry.Results In mice receiving saline injection,the liver volume was nearly restored 9 days after partial hepatectomy,while in mice with D-GaIN and LPS injections,the liver failed to recover the normal volume even at 14 days,showing a significant difference in the liver regeneration rate between them [（22.6±105.93）% vs（9.49±32.55）%,P0.001].Significant degenerative changes of the hepatic cells were found in D-GaIN/LPS-treated group,while only mild inflammatory reaction was observed in saline-treated group after partial hepatectomy.Obvious hepatocyte proliferation was observed at day 7 in saline-treated group but not in D-GaIN/LPS-treated group.Oval cell proliferation in the portal area occurred 3 days after partial hepatectomy in D-GaIN/LPS-treated group.Conclusion D-GaIN and LPS can obviously inhibit hepatocyte regeneration after liver injury in mice.D-GaIN and LPS combined with partial hepatectomy can induce oval cell proliferation.