外源性胆汁酸恢复胆道外引流导致的肝再生障碍及其机制

A study on exogenous bile acid for recovery of liver regeneration disorder caused by external biliary drainage and its mechanism

目的探讨外源性胆汁酸(CA)恢复胆道外引流导致的肝再生障碍及其可能机制。方法 90只健康雄性SD大鼠随机均分为3组,分别设为未引流组(未引流组,n=30)、外引流组(ED组,n=30)、外引流同时补充0.2%外源性胆汁酸组(ED+0.2%CA组,n=30),各组于实验第7天行部分(70%)肝切除,检测各组肝切除术后不同时间点肝组织增殖细胞核抗原Ki-67的表达情况,检测回肠组织成纤维生长因子15(FGF15)蛋白及mRNA表达情况。结果 ED组的FGF15蛋白及mRNA在肝部分切除术后各时段的表达水平均明显低于ED+0.2%CA组和未引流组(P <0.05),其表达总体呈现先上升后下降的趋势,并在24h达到高峰,峰值较ED+0.2%CA组和未引流组明显偏低(P <0.05),而ED+0.2%CA组的FGF15蛋白及mRNA各时段的表达明显低于未引流组,峰值较未引流组明显偏低(P <0.05)。在肝切除术后,ED组与ED+0.2%CA组和未引流组相比,肝组织增殖细胞核抗原(Ki-67)表达水平在48 h和72 h时段明显降低(P <0.05);而ED+0.2%CA组与未引流组相比,肝组织增殖细胞核抗原(Ki-67)水平在48 h时段明显降低(P <0.05)。结论外源性胆汁酸可以部分恢复胆道外引流导致的肝再生延迟,其可能机制是与其上调肠道FGF15的表达从而促进肝再生有关。

Objective To investigate the possible mechanism of exogenous cholic acids(CA)in the recovery of liver regeneration caused disorder by biliary drainage.Methods 90 healthy male SD rats were randomly divided into 3 groups,including non-drainage group(n=30),external drainage group(ED group,n=30),and external drainage plus 0.2%exogenous bile acid group(ED+0.2%CA group,n=30).Partial liver resection(70%)was performed on day 7 for detecting the expression of proliferating cell nuclear antigen(Ki-67)in liver tissue at different time points.Ileal tissues were collected to detect the protein and mRNA expressions of fibroblast growth factor 15(FGF15)in each groups.Results The expression levels of FGF15 protein and mRNA were significantly lower ED group than in both ED+0.2%CA group and non drainage group at different time points after partial hepatectomy(P<0.05);the overall expression showed a downward trend after rising and reaching the peak at 24 hours,with a significantly lower peak value as compared with ED+0.2%CA group and non drainage group(P<0.05),while the expression of FGF15 protein and mRNA at different time points and also the peak value were significantly lower in ED+0.2%CA group than in non drainage group(P<0.05).After liver resection,the expression levels of liver tissue proliferating cell nuclear antigen(Ki-67)were significantly lower in ED group as compared with ED+0.2%CA group and non drainage group at hours 48 and 72(P<0.05);and they were signifi-cantly lower in ED+0.2%CA group at hour 48 as compared with non drainage group(P<0.05).Conclusion Ex-ogenous cholic acid supplement can partially improve liver regeneration disorder caused by external drainage,whose mechanism may be associated with up-regulation of FGF15 expressions,and thereby resulting in promotion of liver regeneration.