Extravasated platelet aggregation in the livers of rats with drug-induced hepatic sinusoidal obstruction syndrome
Extravasated platelet aggregation in the livers of rats with drug-induced hepatic sinusoidal obstruction syndrome
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DOI：
10.3892/mmr.2017.6407
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发表时间：
2017-05-01
影响因子：
3.4
通讯作者：
Ohta, Tetsuo
中科院分区：
文献类型：
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作者：
Hirata, Miki;Tajima, Hidehiro;Ohta, Tetsuo
以奥沙利铂为基础的化疗在结直肠癌肝转移的治疗中发挥着重要作用。然而，奥沙利铂可引起窦阻塞综合征（SOS），其特征为门静脉高压、脾肿大、血小板减少和肝功能障碍。通过窦内皮的破坏、胶原沉积、纤维化（特别是在3区周围）、窦腔的扩张和充血，在组织病理学上诊断SOS。本研究评估了SOS大鼠模型的特征。通过给予野百合碱（MCT）诱导大鼠SOS。比较给予MCT和溶剂（对照组）的大鼠的血液化学以及肉眼和显微镜检查结果。免疫组化分析肝脏中CD 41、P-选择素、大鼠内皮细胞抗原-1、CD 34和裂解的半胱天冬酶-3的表达水平。此外，这些大鼠的肝脏进行了电子显微镜分析。肉眼观察，MCT给药大鼠显示血性腹水和蓝色肝脏蓄积，并在组织学上诊断为SOS。血清谷草转氨酶（P=0.003）、丙氨酸转氨酶（P=0.008）、总胆红素（P=0.012）、直接胆红素（P=0.007）、间接胆红素（P=0.003）、乳酸脱氢酶（P
Oxaliplatin-based chemotherapy plays an important role in the treatment of colorectal liver metastases. Oxaliplatin, however, causes sinusoidal obstruction syndrome (SOS), which is characterized by portal hypertension, splenomegaly, thrombocytopenia, and liver dysfunction. SOS is diagnosed histopathologically by disruption of the sinusoidal endothelium, collagen deposition, fibrosis especially around zone 3, dilatation of the sinusoidal space and congestion. This study assessed the characteristics of a rat model of SOS. SOS was induced in rats by administration of monocrotaline (MCT). Blood chemistries and macroscopic and microscopic findings were compared in rats administered MCT and vehicle (control group). Levels of expression in the liver of CD41, P-selectin, rat endothelial cell antigen-1, CD34, and cleaved caspase-3 were analyzed immunohistochemically. Moreover, livers of these rats were analyzed by electron microscopy. Macroscopically, MCT-treated rats showed accumulation of bloody ascites and blue liver and were diagnosed with SOS histologically. Serum concentrations of aspartate aminotransferase (P=0.003), alanine aminotransferase (P=0.008), total-bilirubin (P=0.012), direct-bilirubin (P=0.007), indirect-bilirubin (P=0.003), lactate dehydrogenase (P