ESTROGEN PROMOTES HEPATIC REGENERATION VIA ACTIVATING SEROTONIN SIGNAL
ESTROGEN PROMOTES HEPATIC REGENERATION VIA ACTIVATING SEROTONIN SIGNAL
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DOI：
10.1097/shk.0b013e31818ec195
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发表时间：
2009-06-01
期刊：
影响因子：
3.1
通讯作者：
Nagino, Masato
中科院分区：
文献类型：
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作者：
Kitagawa, Tomomi;Yokoyama, Yukihiro;Nagino, Masato
本研究的目的是确定雌激素在门静脉分支结扎（PBL）后未结扎肝叶的肝再生过程中是否发挥作用。我们还研究了雌激素是否与肝脏再生过程中的血清素作用有关。使用（E组）或不使用（非E组）雌激素颗粒的卵巢切除雌性大鼠在左叶和中叶进行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手术。在 PBL 后第 1、2 和 7 天，E 组的再生率明显高于非 E 组。 E组肝再生相关基因（如IL-6、TNF-α、肝生长因子、c-fos和c-myc）的激活也显着高于非E组。 E组肝脏中血清素受体（5-HT2A）和小肠中色氨酸羟化酶1的基因表达也上调，表明E组中血清素系统被激活。此外，荧光微球测定的总肠流量、门静脉流量和肝动脉流量在E组中显着高于非E组。此外，血清素受体拮抗剂（酮色林）显着降低了 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着重要作用。我们的结果还表明，雌激素至少部分与血清素系统的激活有关，这在肝脏再生过程中也很重要。
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.