Schiffer Eduardo, Frossard Jean-Louis, Rubbia-Brandt Laura, Mentha Gilles, Pastor Catherine M
Laboratoire de Physiopathologie Hépatique et Imagerie Moléculaire, Hôpitaux Universitaires de Genève, Geneva 1205, Switzerland.
J Surg Oncol. 2009 Jun 1;99(7):439-46. doi: 10.1002/jso.21276.
Oxaliplatin is a chemotherapeutic drug for colorectal adenocarcinoma able to extend the indications for resection of colorectal liver metastases. However, the drug may severely injure hepatic sinusoids, inducing a sinusoidal obstruction syndrome in non-tumoral parenchyma with a risk of decreased regeneration in the remnant liver following partial hepatectomy.
We then investigated the evolution of hepatic functions and liver regeneration following partial hepatectomy in rats with sinusoidal obstruction syndrome. The sinusoidal obstruction syndrome was induced with a single intragastric administration of monocrotaline (MCT).
MCT administration induced obstruction of the hepatic microcirculation and increased portal pressure, hepatic VEGF expression, and Ki67 positive hepatocytes. A mild cholestasis was present without modification of hepatic tests. Following a 70% hepatectomy, liver regeneration was significantly impaired by MCT administration and this impaired regeneration was associated with hepatocellular injury evidenced 1 week after hepatectomy.
The presence of sinusoidal obstruction syndrome impairs hepatic regeneration in this rat model of sinusoidal obstruction syndrome.
奥沙利铂是一种用于治疗结肠腺癌的化疗药物，能够扩大结肠肝转移瘤切除术的适应症。然而，该药物可能会严重损伤肝血窦，在非肿瘤实质中诱发肝窦阻塞综合征，存在肝部分切除术后残余肝脏再生能力下降的风险。
我们随后研究了肝窦阻塞综合征大鼠肝部分切除术后肝功能及肝脏再生的变化情况。通过单次胃内注射野百合碱（MCT）诱导肝窦阻塞综合征。
注射MCT导致肝微循环阻塞，门静脉压力升高，肝脏VEGF表达增加，Ki67阳性肝细胞增多。出现轻度胆汁淤积，但肝功能检查无变化。70%肝切除术后，MCT给药显著损害肝脏再生，这种再生受损与肝切除术后1周出现的肝细胞损伤有关。
在该肝窦阻塞综合征大鼠模型中，肝窦阻塞综合征的存在会损害肝脏再生。
