Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
J Surg Res. 2010 Jun 15;161(2):328-35. doi: 10.1016/j.jss.2009.02.013. Epub 2009 Mar 20.
To investigate hepatic regenerative response and associated mechanisms in different-size liver grafts in the rat.
Rat models of different-size-graft liver transplantation (whole, 50%-size, or 30%-size) were established, with a sham operation group serving as a control. Portal pressure, graft injury, interleukin 6 (IL-6), signal transducer and activator of transcription (Stat3), mitogen-activated protein kinase (MAPK), cyclin D1, and proliferating cell nuclear antigen (PCNA) were all assessed.
The portal pressure was significantly higher and hepatic injury more severe in the smaller sized groups than in the whole graft group, especially in the 30%-size grafts. Hepatic IL-6 and tumor necrosis factor-alpha (TNF-alpha) levels in the two smaller sized groups were significantly higher than in the whole graft group, while IL-6 levels appeared to be negatively associated with graft sizes. Downstream markers of IL-6, Stat3 and MAPK phosphorylation, cyclin D1, and PCNA expression were also markedly increased in the small-sized grafts compared with the whole grafts, and appeared to positively correlate with early measurements of portal pressure and subsequent hepatic injury.
Vigorous hepatic regeneration in small-for-size liver grafts may be associated with highly activated IL-6/Stat3 and MAPK signaling, which may in turn correlate with graft size, portal pressure, and hepatic injury.
研究大鼠不同大小肝移植物中的肝再生反应及相关机制。
建立大鼠不同大小肝移植（全肝、50%大小或 30%大小）模型，以假手术组作为对照。评估门静脉压力、移植物损伤、白细胞介素 6（IL-6）、信号转导和转录激活因子 3（Stat3）、丝裂原活化蛋白激酶（MAPK）、细胞周期蛋白 D1 和增殖细胞核抗原（PCNA）。
与全肝组相比，较小体积组的门静脉压力明显升高，肝损伤更严重，尤其是 30%体积组。两个较小体积组的肝 IL-6 和肿瘤坏死因子-α（TNF-α）水平明显高于全肝组，而 IL-6 水平似乎与移植物体积呈负相关。较小体积组的下游 IL-6 标志物 Stat3 和 MAPK 磷酸化、细胞周期蛋白 D1 和 PCNA 表达也明显高于全肝组，且与早期门静脉压力和随后的肝损伤呈正相关。
小体积肝移植物中的强烈肝再生可能与高度激活的 IL-6/Stat3 和 MAPK 信号通路有关，而该信号通路可能与移植物体积、门静脉压力和肝损伤相关。
