Single Administration of Thrombopoietin Prevents Progression of Liver Fibrosis and Promotes Liver Regeneration After Partial Hepatectomy in Cirrhotic Rats
Single Administration of Thrombopoietin Prevents Progression of Liver Fibrosis and Promotes Liver Regeneration After Partial Hepatectomy in Cirrhotic Rats
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DOI：
10.1097/sla.0b013e31818584c7
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发表时间：
2008-11-01
影响因子：
9
通讯作者：
Hkohchi, Nobuhiro
中科院分区：
文献类型：
--
作者：
Murata, Soichiro;Hashimoto, Ikuka;Hkohchi, Nobuhiro
目的：为了评价血小板生成素对大鼠肝切除术后肝再生和肝硬化条件下抗纤维化的作用，我们揭示了血小板生成素给药诱导的血小板促进正常肝切除术后的肝再生。（1）正常对照组，（2）肝硬化（LC）组，（3）血小板生成素联合肝硬化（LC+TPO）组，（4）血小板生成素、抗血小板血清联合肝硬化（LC+TPO+APS）组。分析肝再生的生长动力学和生长因子。结果：LC组术后24 h肝再生较正常组明显延迟，肝纤维化面积明显缩小，肝星状细胞活化程度明显降低。另一方面，与LC组相比，LC+TPO组的肝再生显著增加，达到与正常组相同的水平。LC组术前肝纤维化面积明显高于正常组。LC+TPO组肝纤维化程度较LC组明显减轻。LC +TPO+APS组的抗肝纤维化和促肝再生作用可被抗血小板血清所抑制。结论：血小板生成素可通过增加血小板在肝切除术后的聚集，减轻肝纤维化，促进肝再生。这可能是一种潜在的有用的治疗肝硬化。
Objective: To evaluate the effect of thrombopoietin on liver regeneration after hepatectomy and antifibrosis under conditions of liver cirrhosis in rats.Summary Background Data: We revealed that platelets induced by thrombopoietin administration promote liver regeneration after hepatectomy in the normal liver.Methods: Seventy percent hepatectomy was carried out in rats, which were subsequently divided into 4 groups: (1) normal group without any treatment, (2) liver cirrhosis (LC) group, (3) combined thrombopoietin and liver cirrhosis (LC+TPO) group, and (4) combined thrombopoietin, antiplatelet serum and liver cirrhosis (LC+TPO+APS) group. Growth kinetics in the liver regeneration and growth factors were analyzed. Liver fibrotic area and activation of hepatic stellate cells were also investigated.Results: In LC group, liver regeneration was significantly delayed compared with normal group 24 hours after hepatectomy. On the other hand, liver regeneration of LC+TPO group increased significantly compared with LC group, to a level that was the same as that recorded in normal group. In LC group, liver fibrotic area before hepatectomy was significantly higher compared with the normal group. Liver fibrosis of LC+TPO group was significantly reduced compared with LC group. The antifibrotic and liver regeneration promoting effects of LC+TPO group were inhibited by antiplatelet serum in LC+TPO+APS group.Conclusion: The administration of thrombopoietin reduces liver fibrosis and stimulates regeneration after hepatectomy through increment and accumulation of platelets in the cirrhotic liver. This could be a potentially useful treatment for liver cirrhosis.