ActivinA抑制卵圆细胞介导肝再生的体内研究

Activin A suppressed hepatic oval cell-mediated liver regeneration in vivo

目的研究ActivinA对卵圆细胞介导肝再生的抑制作用及其机制。方法建立2一乙酰胺基芴／部分肝切除卵圆细胞介导肝再生模型，肝切除后立即经门静脉注射1μg Activin A（ActivinA组），或生理盐水（对照组）。肝切除后不同时间点取肝脏标本检测卵圆细胞增殖及肝再生率和磷酸化smad2，p15和p21的表达。结果ActivinA组肝脏中卵圆细胞的增殖及肝再生率均明显低于对照组；ActivinA组肝脏中smad2的磷酸化水平及p15，p21的表达水平均高于对照组。结论ActivinA可以通过smad信号通路抑制卵圆细胞介导的肝再生。

Objective To study the inhibitory effect and mechanism of Activin A on hepatic oval cell-mediated liver regeneration. Methods 2-acetylaminofluorene/partial hepatectomy （2-AAF/PH） oval cell-mediated liver regeneration model was established. One μg Activin A （Activin A group） or normal saline （control S group） was infused into portal vein immediately after 70 % partial hepatectomy. Animals were sacrificed at 2nd, 4th, 6th, and 9th day after hepatectomy. Liver regeneration rate was measured. Changes in Pan-CK positive oval cell number and nuclear bromodeoxyuridine labeling were detected by using immunohistochemistry. The expression of phosphorylated smad2, p15,and p21 were detected by using Western blotting. Results As compared with control group, the Pan-CK positive number was significantly reduced in Activin A group at 6th and 9th day after hepatectomy, and Brdu labeling nuclear number was reduced in Activin A group at 4th,6th and 9th day after hepatectomy. The liver regeneration rate in Activin A group was lower than in control group. Higher levels of phosphorylated smad2,pl5 and p21 were detected in Activin A group. Conclusion Activin A could suppress oval cell-mediated liver regeneration through smad pathway-dependent up-regulation of p15 and p21.