贝伐珠单抗并不抑制肝大部切除术后肝脏血管的形成和肝脏再生：一项大动物模型研究。
Bevacizumab Does Not Inhibit the Formation of Liver Vessels and Liver Regeneration Following Major Hepatectomy: A Large Animal Model Study.
机构信息
Department of Plastic Surgery, Medical School and Teaching Hospital in Pilsen, Charles University, Pilsen, Czech Republic.
Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
出版信息
In Vivo. 2022 May-Jun;36(3):1083-1094. doi: 10.21873/invivo.12806.
BACKGROUND/AIM: Patients with unresectable liver colorectal cancer metastases are treated with neoadjuvant chemotherapy often accompanied by biological therapy aimed at reducing the mass of metastases and thus increasing the chances of resectability. Bevacizumab comprises an anti-VEGF (vascular endothelial growth factor) humanized IgG monoclonal antibody that is used for biological therapy purposes. It acts to inhibit angiogenesis, thereby slowing down the growth of metastases. Due to its being administered systematically, bevacizumab also exerts an effect on the surrounding healthy liver parenchyma and potentially limits the process of neovascularization and thus regeneration of the liver. Since the remnant liver volume forms an important factor in postoperative morbidity and mortality following a major hepatectomy, we decided to study the effect of bevacizumab on vascular and biliary microarchitecture in healthy liver parenchyma and its ability to regenerate following major hepatectomy.
MATERIALS AND METHODS
We performed an experiment employing a large animal model where a total of 16 piglets were divided into two groups (8 piglets in the control group and 8 piglets in the experimental group with bevacizumab). All the animals were subjected to major hepatectomy and the experimental group was given bevacizumab prior to hepatectomy. All the animals were sacrificed after 4 weeks. We performed biochemical analyses at regular time intervals during the follow-up period. Histological examination of the liver tissue was performed following sacrifice of the animals.
RESULTS
No statistical difference was shown between groups in terms of the biochemical and immunohistochemical parameters. The histological examination of the regenerating liver tissue revealed the higher length density of sinusoids in the experimental group.
CONCLUSION
Bevacizumab does not act to impair liver regeneration following hepatectomy.
背景/目的：对于无法切除的结直肠癌肝转移患者，通常采用新辅助化疗联合生物治疗，目的是减少转移灶的体积，从而提高可切除性。贝伐珠单抗是一种抗血管内皮生长因子（VEGF）的人源化 IgG 单克隆抗体，用于生物治疗。它通过抑制血管生成来减缓转移灶的生长。由于其系统给药，贝伐珠单抗还会对周围健康的肝实质产生影响，并可能限制新生血管形成和肝再生的过程。由于残肝体积是肝叶切除术术后发病率和死亡率的重要因素，我们决定研究贝伐珠单抗对健康肝实质的血管和胆管微结构的影响及其在肝叶切除术后的再生能力。
材料和方法
我们进行了一项大型动物实验，共有 16 头小猪分为两组（对照组 8 头，贝伐珠单抗实验组 8 头）。所有动物均接受了大范围肝切除术，实验组在肝切除术前给予贝伐珠单抗。所有动物在 4 周后被处死。我们在随访期间定期进行生化分析。动物死后进行肝脏组织的组织学检查。
结果
两组间的生化和免疫组化参数无统计学差异。对再生肝组织的组织学检查显示实验组的窦状隙长度密度较高。
结论
贝伐珠单抗不会影响肝叶切除术后的肝再生。
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