Kitagawa Tomomi, Yokoyama Yukihiro, Kokuryo Toshio, Kawai Toru, Watanabe Katsutaka, Kawai Kiyotaka, Nagino Masato
Department of Surgery, Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Shock. 2009 Jun;31(6):615-20. doi: 10.1097/SHK.0b013e31818ec195.
The aim of this study was to determine if estrogen plays any role in the process of hepatic regeneration of nonligated lobe after portal vein branch ligation (PBL). We also investigated whether estrogen has any association with serotonin action during liver regeneration. Ovariectomized female rats with (E group) or without (non-E group) estrogen pellet were subjected to PBL on the left and middle lobes. Thereafter, the rats were killed, and blood, liver, and small intestine were sampled and analyzed. Sham animals underwent only ovariectomy and laparotomy. The E group showed a significantly greater regeneration rate than the non-E group at days 1, 2, and 7 after PBL. The activation of hepatic regeneration-related genes (such as IL-6, TNF-alpha, hepatic growth factor, c-fos, and c-myc) was also significantly higher in the E group as compared with the non-E group. Gene expression of serotonin receptor (5-HT2A) in the liver and tryptophan hydroxylase 1 in the small intestine were also up-regulated in the E group, indicating an activation of serotonin system in the E group. Additionally, total intestinal flow, portal venous flow, and hepatic arterial flow determined by fluorescent microsphere were significantly higher in the E group compared with the non-E group. Moreover, serotonin receptor antagonist (ketanserin) significantly attenuated liver regeneration rate in the E group. These results indicated that estrogen plays an important role in the process of liver regeneration after PBL. Our results also indicated that estrogen is at least partly related to the activation of serotonin system, which is also important in the process of liver regeneration.
本研究的目的是确定雌激素在门静脉分支结扎（PBL）后非结扎叶肝再生过程中是否发挥任何作用。我们还研究了雌激素在肝脏再生过程中是否与5-羟色胺作用相关。对切除卵巢的雌性大鼠，植入（E组）或未植入（非E组）雌激素微丸，然后对其左叶和中叶进行PBL。此后，处死大鼠，采集血液、肝脏和小肠样本并进行分析。假手术动物仅接受卵巢切除术和剖腹术。在PBL后第1、2和7天，E组的再生率显著高于非E组。与非E组相比，E组中肝再生相关基因（如IL-6、TNF-α、肝生长因子、c-fos和c-myc）的激活也显著更高。E组肝脏中5-羟色胺受体（5-HT2A）和小肠中色氨酸羟化酶1的基因表达也上调，表明E组中5-羟色胺系统被激活。此外，通过荧光微球测定的总肠血流量、门静脉血流量和肝动脉血流量，E组显著高于非E组。此外，5-羟色胺受体拮抗剂（酮色林）显著降低了E组的肝再生率。这些结果表明，雌激素在PBL后的肝再生过程中发挥重要作用。我们的结果还表明，雌激素至少部分与5-羟色胺系统的激活有关，而这在肝再生过程中也很重要。
