The effects of sorafenib on liver regeneration in a model of partial hepatectomy.
The effects of sorafenib on liver regeneration in a model of partial hepatectomy.
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索拉非尼对部分肝切除模型中肝再生的影响。
DOI：
10.1016/j.jss.2012.01.033
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Katz,StevenC
中科院分区：
文献类型：
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作者：
Kurniali,PeterC;O'Gara,Katie;Wang,Xiaofei;Wang,LiJuan;Somasundar,Ponnandai;Falanga,Vincent;Espat,NJoseph;Katz,StevenC
索拉非尼目前已被批准用于晚期肝细胞癌（HCC），目前正在研究作为HCC切除术后的辅助治疗。索拉非尼对肝再生的影响尚未明确定义。我们的目的是确定索拉非尼对小鼠部分肝切除术（PH）model.MATERIALS和METHODSWe肝再生的影响索拉非尼治疗的范围索拉非尼剂量与评估在几个时间点在C57 B1/6小鼠进行PH。采用流式细胞术和免疫组织化学方法，用5-溴-2 ′-脱氧尿苷（BrdU）和Ki 67检测肝窦内皮细胞（LSEC）和肝细胞DNA合成和增殖。用60 mg/kg索拉非尼治疗后，PH后48小时非纤维化LSEC有统计学显著增加。然而，在任何其他剂量或时间点，索拉非尼均未显著影响LSEC和肝细胞中的BrdU和Ki 67染色。BrdU和Ki 67流式细胞术数据与免疫组化结果和术后肝weights.CONCLUSIONIn小鼠PH模型，索拉非尼没有改变正常或纤维化肝脏PH后的修复反应，测量肝脏重量，DNA合成和细胞增殖的变化。这些结果表明，肝切除术后给予索拉非尼不会损害肝再生。
BACKGROUNDSorafenib is currently approved for advanced hepatocellular carcinoma (HCC) and is presently being studied as an adjuvant treatment for HCC following resection. The effects of sorafenib on liver regeneration have not been clearly defined. Our objective was to identify the effects of sorafenib on liver regeneration in a murine partial hepatectomy (PH) model.MATERIALS AND METHODSWe performed PH in C57Bl/6 mice treated with a range of sorafenib doses with assessments at several time points. Liver sinusoidal endothelial cells (LSEC) and hepatocyte DNA synthesis and proliferation were assessed with 5-bromo-2′-deoxyuridine (BrdU) and Ki67 by flow cytometry and immunohistochemistry.RESULTSTreatment with sorafenib did not result in any deaths following PH. When we measured BrdU uptake to assess DNA synthesis, there was a statistically significant increase at 48 h post-PH for nonfibrotic LSEC following treatment with 60 mg/kg of sorafenib. However, BrdU and Ki67 staining among LSEC and hepatocytes was not significantly affected by sorafenib at any of the other doses or time points. BrdU and Ki67 flow cytometry data correlated with immunohistochemistry findings and postoperative liver weights.CONCLUSIONIn a murine PH model, sorafenib did not alter the repair response of normal or fibrotic livers following PH as measured by changes in liver weight, DNA synthesis, and cellular proliferation. These findings suggest sorafenib administered following hepatic resection does not impair liver regeneration.