胆汁酸在梗阻性黄疸小鼠肝部分切除术后肝再生中作用 的研究
| 作者: |
1胡亿龙,
1周毅,
2袁晟光
1 桂林医学院，广西 桂林 541001 2 桂林医学院附属医院 肝胆胰外科，广西 桂林 541001 |
| 通讯: |
袁晟光
Email: ysg518@qq.com |
| DOI: | 10.3978/.10.3978/j.issn.1005-6947.2015.07.011 |
| 基金: | 广西自然科学基金资助项目, 2013GXNSFAA019196 广西医学科学实验中心开放基金资助项目, KFJJ2011-08 |
摘要
目的：探讨胆汁酸（CA）在梗阻性黄疸（OJ）小鼠肝部分切除术后肝再生中的作用及机制。方法：180 只健康雄性小鼠随机均分为6 组，分别行假手术（对照组）、胆总管结扎（OJ 组）、胆总管结扎并于7 d 加行外引流（ED 组）、胆总管结扎+0.2%CA 灌胃并7 d 后加行外引流（ED+0.2%CA 组）、胆总管结扎+1%CA 灌胃并于7 d 后加行外引流（ED+1%CA 组）、胆总管结扎并于7 d 后加行内引流（ID 组），各组分别于实验第14 天行70% 肝切除，且各外引流组改行内引流。检测各组肝切除术后不同时间点肝再生率与肝组织增殖细胞核抗原Ki-67 表达、叉状头盒M1b 基因（Foxm1b）mRNA 相对表达、成纤维细胞生长因子受体4（FGFR4）蛋白表达，并观察部分组肝细胞原位凋亡情况。结果：除对照组外，肝再生率、肝组织Ki-67 阳性表达率、Foxm1b mRNA 及FGFR4 蛋白表达在其余各组均由高到低依次为：ID 组>ED+0.2%CA 组>ED 组>OJ 组>ED+1%CA 组，组间差异均有统计学意义（均P<0.05）；ID 组与对照组间各指标差异均无统计学意义（均P>0.05）；肝细胞凋亡率由高到低依次为：ED+1%C 组>ED 组>ED+0.2%CA 组> 对照组，组间差异均有统计学意义（均P<0.05）。结论：内引流通过减少内源性CA 的丢失有利于肝切除后肝再生；外源性低浓度CA 可以恢复外引流引起的肝再生障碍，可能与其上调Foxm1b 与FGFR4 的表达从而促进肝再生有关
关键词：
肝切除术
胆汁酸
肝再生
黄疸，阻塞性
引流术
Function of cholic acid in liver regeneration of obstructive jaundice following partial hepatectomy in mice
CorrespondingAuthor:YUAN Shengguang Email: ysg518@qq.com
Abstract
Objective: To investigate the function of cholic acid (CA) in liver regeneration of obstructive jaundice (OJ) following partial hepatectomy in mice and the mechanism. Methods: One hundred and eighty healthy male mice were equally randomized into 6 groups, and underwent sham operation (control group), common bile duct ligation (OJ group), common bile duct ligation followed by external drainage (ED)7 d later (ED group), common bile duct ligation plus 0.2%CA gavage followed by ED 7 d later (ED+0.2%CA group), common bile duct ligation plus 1%CA gavage followed by ED 7 d later (ED+1%CA group), and common bile duct ligation followed by internal drainage (ID) 7 d later (ID group), respectively. In the 14th day of experiment, partial (70%) liver resection was performed in each group of mice, and ID conversion was made in each group of mice with ED treatment. On different time points after hepatecomy, the liver regeneration rate and expression of proliferation-associated nuclear antigen Ki-67, mRNA expression of forkhead box M1b (Foxm1b), and protein expression of fibroblast growth factor receptor 4 (FGFR4) in the liver tissue were determined, and in situ apoptosis of hepatic cells was also observed in some of the groups. Results: Excluding the control group, the liver regeneration rate, Ki-67 positive expression rate, and Foxm1b mRNA as well as FGFR4 protein expression levels in the remaining groups were all presented in a decreasing order as follows: ID group>ED+0.2%CA group>ED group>OJ group>ED+1%CA group, and all inter-group differences had statistical significance (all P<0.05); there was no significant difference in any of the above parameters between ID group and control group (all P>0.05). The apoptosis rate of hepatic cells showed a decreasing order as follows: ED+1%CA group>ED group>ED+0.2%CA group>control group, and all inter-group differences had statistical significance (all P<0.05). Conclusion: ID is beneficial to liver regeneration after liver resection through reducing endogenous CA loss; low concentration of exogenous CA supplement can improve the liver regeneration retardation caused by ED, which may be associated with its up-regulating Foxm1b and FGFR4 expressions, and thereby promote liver regeneration.
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