Endothelial-directed hepatic regeneration after partial hepatectomy
Endothelial-directed hepatic regeneration after partial hepatectomy
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DOI：
10.1097/00000658-200304000-00015
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发表时间：
2003-04-01
影响因子：
9
通讯作者：
O'Reilly, MS
中科院分区：
文献类型：
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作者：
Greene, AK;Wiener, S;O'Reilly, MS
目的 确定微血管内皮在部分肝切除术后肝脏质量再生调节中的作用摘要背景数据血管生成对于病理和生理过程都至关重要。人们对某些组织（例如肝脏、肾脏和脾脏）受伤后的再生能力知之甚少。手术切除后 8 天内，肝脏将再生至正常质量。因为作者之前已经证明内皮细胞调节肿瘤质量，所以我们假设正常成人器官质量也受内皮细胞控制。方法对 7 至 8 周龄的 C57 BL/6 小鼠进行三分之二部分肝切除术，然后用血管生成刺激剂碱性成纤维细胞生长因子 (bFGF)（1 微克/克/天腹膜内注射）或血管生成抑制剂进行全身治疗TNP-470（30 mg/kg/qod 皮下注射）。然后在术后第 2、4、6 和 8 天对三只小鼠进行安乐死，对肝脏进行称重并进行免疫组织化学分析。结果 bFGF 在术后第 2、4、6 和 8 天分别加速肝脏再生 42%、19%、16% 和 16%。 TNP-470 在术后第 2、4、6 和 8 天分别抑制肝再生 46%、74%、67% 和 64%。免疫组织化学显示 bFGF 和 TNP-470 主要影响内皮区室。具体来说，bFGF 增加内皮增殖并减少内皮细胞凋亡。相反，TNP-470 抑制内皮细胞增殖。再生过程的停止与内皮增殖的减少和内皮细胞凋亡的增加相关。结论血管生成剂的全身施用主要通过影响内皮细胞增殖或凋亡来调节肝块的再生。内皮细胞凋亡与对照小鼠再生过程的停止相关。这些结果表明，内皮细胞是部分肝切除模型中成人组织块再生的关键介质之一。
Objective To determine the role of the microvascular endothelium in the regulation of regenerating liver mass after partial hepatectomySummary Background Data Angiogenesis is critical for both pathologic and physiologic processes. The ability of certain tissues, such as the liver, kidney, and spleen, to regenerate after injury is poorly understood. The liver will regenerate to its normal mass within 8 days of surgical excision. Because the authors have previously shown that the endothelial cell regulates tumor mass, we hypothesized that normal adult organ mass is also controlled by the endothelial cell.Methods Two-thirds partial hepatectomy was performed in 7- to 8-week-old C57 BL/6 mice, followed by systemic treatment with either the angiogenesis stimulator basic fibroblast growth factor (bFGF) (1 mug/g/d intraperitoneal) or the angiogenesis inhibitor TNP-470 (30 mg/kg/qod subcutaneous). Groups of three mice were then euthanized on postoperative days 2, 4, 6, and 8, and the livers were weighed and analyzed by immunohistochemistry.Results bFGF accelerated hepatic regeneration by 42%, 19%, 16%, and 16% on postoperative days 2, 4, 6, and 8, respectively. TNP-470 inhibited hepatic regeneration by 46%, 74%, 67%, and 64% on postoperative days 2, 4, 6, and 8, respectively. Immunohistochemistry revealed that bFGF and TNP-470 primarily affected the endothelial compartment. Specifically, bFGF increased endothelial proliferation and decreased endothelial apoptosis. TNP-470, in contrast, inhibited endothelial cell proliferation. The cessation of the regenerative process correlated with a decrease in endothelial proliferation and an increase in endothelial apoptosis.Conclusions The systemic administration of anigiogenesis agents modulates the regeneration of hepatic mass primarily by affecting endothelial cell proliferation or apoptosis. Endothelial cell apoptosis is associated with the cessation of the regenerative process in control mice. These results suggest that the endothelial cell is one of the key mediators of regenerating adult tissue mass in this partial hepatectomy model.