Department of General Surgery, Medical School, Hacettepe University, Ankara, Turkey.
Surgery. 2010 Feb;147(2):288-94. doi: 10.1016/j.surg.2009.10.015. Epub 2009 Dec 11.
The aim of this study was to evaluate the antiangiogenic response and its relation to regeneration and angiogenesis after 70% hepatectomy in a rat model.
Sixty-four Wistar albino rats were included in the study. Animals were allocated into 8 groups (n = 8). After a 70% hepatectomy, liver regeneration, angiogenesis, and antiangiogenic response were evaluated in the remnant liver on days 0, 1, 2, 3, 5, 7, 10, and 14. Regeneration and angiogenesis were determined with immunoreactivity to proliferating cell nuclear antigen and vascular endothelial growth factor. Antiangiogenic response was evaluated by detecting collagen 18 m RNA with reverse transcriptase polymerase chain reaction.
We showed that liver regeneration peaked at day 1, whereas angiogenesis in the periportal and perisinusoidal areas reached their peak values on days 3 and 7, respectively. Both regeneration and angiogenic activity around perisinusoidal hepatocytes returned to basal activity on the day 10. Antiangiogenic response first appeared on day 5, reached a peak on day 10, and returned to basal values on day 14.
Collagen18 mRNA expression is present in the normal liver during the regenerative process. We suggest that the stimulus that causes the cessation of regeneration process may come from hepatocytes, and collagen 18 produced by hepatocytes may modulate this event by inhibiting the angiogenesis.
本研究旨在评估抗血管生成反应及其与大鼠模型 70%肝切除后再生和血管生成的关系。
将 64 只 Wistar 白化大鼠纳入研究。动物分为 8 组(n = 8)。在 70%肝切除后,在第 0、1、2、3、5、7、10 和 14 天评估残肝的肝再生、血管生成和抗血管生成反应。通过增殖细胞核抗原和血管内皮生长因子的免疫反应性来确定再生和血管生成。通过逆转录聚合酶链反应检测胶原 18 m RNA 来评估抗血管生成反应。
我们表明肝再生在第 1 天达到峰值,而门静脉周围和窦周区域的血管生成分别在第 3 天和第 7 天达到峰值。围绕窦周肝细胞的再生和血管生成活性在第 10 天恢复到基础水平。抗血管生成反应于第 5 天首次出现,于第 10 天达到峰值,于第 14 天恢复到基础水平。
胶原 18 mRNA 在肝再生过程中存在于正常肝脏中。我们认为,导致再生过程停止的刺激可能来自肝细胞,而肝细胞产生的胶原 18 通过抑制血管生成来调节这一事件。