Murata Soichiro, Hashimoto Ikuka, Nakano Yoritaka, Myronovych Andriy, Watanabe Motonobu, Ohkohchi Nobuhiro
Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
Ann Surg. 2008 Nov;248(5):821-8. doi: 10.1097/SLA.0b013e31818584c7.
To evaluate the effect of thrombopoietin on liver regeneration after hepatectomy and antifibrosis under conditions of liver cirrhosis in rats.
We revealed that platelets induced by thrombopoietin administration promote liver regeneration after hepatectomy in the normal liver.
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.
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.
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.
评估血小板生成素对大鼠肝硬化条件下肝切除术后肝再生及抗纤维化的作用。
我们发现,给予血小板生成素诱导产生的血小板可促进正常肝脏肝切除术后的肝再生。
对大鼠进行70%肝切除术,随后将其分为4组:(1)未作任何处理的正常组;(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及生长因子。同时研究肝纤维化面积及肝星状细胞的活化情况。
肝切除术后24小时,LC组的肝再生与正常组相比显著延迟。另一方面,LC+TPO组的肝再生与LC组相比显著增加,达到了与正常组相同的水平。肝切除术前,LC组的肝纤维化面积显著高于正常组。LC+TPO组的肝纤维化与LC组相比显著减轻。LC+TPO+APS组中抗血小板血清抑制了LC+TPO组的抗纤维化及促进肝再生作用。
给予血小板生成素可通过增加和聚集肝硬化肝脏中的血小板来减轻肝纤维化并刺激肝切除术后的肝再生。这可能是一种对肝硬化有潜在治疗作用的方法。