Chen Miao-Yan, Cai Jian-Ting, Du Qin, Wang Liang-Jing, Chen Jia-Min, Shao Li-Ming
Department of Gastroenterology and Hepatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Hepatobiliary Pancreat Dis Int. 2008 Aug;7(4):395-400.
Hepatic veno-occlusive disease (HVOD) is a severe complication of chemotherapy before hematopoietic stem cell transplantation and dietary ingestion of pyrrolizidine alkaloids. Many experimental models were established to study its mechanisms or therapy, but few are ideal. This work aimed at evaluating a rat model of HVOD induced by monocrotaline to help advance research into this disease.
Thirty-two male rats were randomly classified into 5 groups, and PBS or monocrotaline was administered (100 mg/kg or 160 mg/kg). They were sacrificed on day 7 (groups A, B and D) or day 10 (groups C and E). Blood samples were collected to determine liver enzyme concentrations. The weight of the liver and body and the amount of ascites were measured. Histopathological changes of liver tissue on light microscopy were assessed by a modified Deleve scoring system. The positivity of proliferating cell nuclear antigen (PCNA) was estimated.
The rats that were treated with 160 mg/kg monocrotaline presented with severe clinical symptoms (including two deaths) and the histopathological picture of HVOD. On the other hand, the rats that were fed with 100 mg/kg monocrotaline had milder and reversible manifestations. Comparison of the rats sacrificed on day 10 with those sacrificed on day 7 showed that the positivity of PCNA increased, especially that of hepatocytes.
Monocrotaline induces acute, dose-dependent HVOD in rats. The model is potentially reversible with a low dose, but reliable and irreversible with a higher dose. The modified scoring system seems to be more accurate than the traditional one in reflecting the histopathology of HVOD. The enhancement of PCNA positivity may be associated with hepatic tissue undergoing recovery.
肝静脉闭塞病（HVOD）是造血干细胞移植前化疗及饮食摄入吡咯里西啶生物碱所致的严重并发症。已建立了许多实验模型来研究其机制或治疗方法，但理想的模型较少。本研究旨在评估由野百合碱诱导的大鼠HVOD模型，以推动对该疾病的研究。
将32只雄性大鼠随机分为5组，分别给予磷酸盐缓冲液（PBS）或野百合碱（100 mg/kg或160 mg/kg）。在第7天（A、B和D组）或第10天（C和E组）处死大鼠。采集血样以测定肝酶浓度。测量肝脏和身体重量以及腹水量。采用改良的Deleve评分系统评估肝组织光镜下的组织病理学变化。评估增殖细胞核抗原（PCNA）的阳性率。
给予160 mg/kg野百合碱的大鼠出现严重的临床症状（包括2只死亡）及HVOD的组织病理学表现。另一方面，给予100 mg/kg野百合碱的大鼠表现较轻且具有可逆性。第10天处死的大鼠与第7天处死的大鼠相比，PCNA阳性率增加，尤其是肝细胞的阳性率。
野百合碱可诱导大鼠发生急性、剂量依赖性的HVOD。低剂量时该模型可能具有可逆性，但高剂量时可靠且不可逆。改良评分系统在反映HVOD组织病理学方面似乎比传统评分系统更准确。PCNA阳性率的升高可能与肝组织恢复有关。
