Murata Soichiro, Matsuo Ryota, Ikeda Osamu, Myronovych Andriy, Watanabe Motonobu, Hisakura Katsuji, Nakano Yoritaka, Hashimoto Ikuka, Ohkohchi Nobuhiro
Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
World J Surg. 2008 Jun;32(6):1088-96. doi: 10.1007/s00268-008-9493-0.
Platelets have been proven to promote liver regeneration after hepatectomy. Kupffer cells produce inflammatory cytokines and also promote liver regeneration. In the present study, we examined whether platelets promote liver regeneration after hepatectomy under conditions of Kupffer cell depletion.
Seventy percent hepatectomy was carried out in mice, which were subsequently divided into four groups: (1) a normal group without any treatment, (2) a Kupffer cell depleted (KD) group, (3) a thrombocytotic group, and (4) a combined thrombocytotic and Kupffer cell depleted (TKD) group. Growth kinetics in the liver regeneration, growth factors, inflammatory cytokines, and signal transduction relating to hepatocyte proliferation were analyzed.
In the KD group, liver regeneration was significantly delayed compared to the normal group 48 h after hepatectomy. On the other hand, liver regeneration of the TKD group increased significantly compared to KD group, to a level that was the same as that recorded in the normal group. In the thrombocytotic group, liver regeneration increased significantly compared to the normal group. Tumor necrosis factor alpha (TNF-alpha) expression was lower in the KD and TKD groups than in the normal group after hepatectomy, but, in the TKD group, hepatocyte growth factor and Akt phosphorylation were higher than in the normal and KD groups.
After hepatectomy, liver regeneration in the Kupffer cell depleted group was delayed because of lower TNF-alpha expression. Platelets promote liver regeneration even under condition of Kupffer cell depletion by stimulating hepatocyte growth factor and insulin-like growth factor-1 expression, and they activate Akt.
血小板已被证实在肝切除术后可促进肝脏再生。库普弗细胞可产生炎性细胞因子，也能促进肝脏再生。在本研究中，我们检测了在库普弗细胞缺失的情况下，血小板是否能在肝切除术后促进肝脏再生。
对小鼠进行70%肝切除术，随后将其分为四组：（1）未进行任何处理的正常组；（2）库普弗细胞缺失（KD）组；（3）血小板增多组；（4）血小板增多与库普弗细胞缺失联合（TKD）组。分析肝脏再生中的生长动力学、生长因子、炎性细胞因子以及与肝细胞增殖相关的信号转导。
在肝切除术后48小时，KD组的肝脏再生与正常组相比显著延迟。另一方面，TKD组的肝脏再生与KD组相比显著增加，达到与正常组相同的水平。血小板增多组的肝脏再生与正常组相比显著增加。肝切除术后，KD组和TKD组的肿瘤坏死因子α（TNF-α）表达低于正常组，但在TKD组中，肝细胞生长因子和Akt磷酸化高于正常组和KD组。
肝切除术后，库普弗细胞缺失组的肝脏再生因TNF-α表达降低而延迟。即使在库普弗细胞缺失的情况下，血小板通过刺激肝细胞生长因子和胰岛素样生长因子-1的表达促进肝脏再生，并激活Akt。
