Guo Jian-wen, Xi Dong, Yan Wei-ming, Luo Xiao-ping, Ning Qin
Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Zhonghua Gan Zang Bing Za Zhi. 2009 Sep;17(9):691-4.
To establish a pig model of fulminant hepatic failure for evaluating the pre-clinical efficacy of drug treatment on severe hepatitis, and to detect the expression of fibrinogen-like protein-2 (fgl2) prothrombinase in the model, so as to provide basis for gene therapy targeting to fgl2 for fulminant hepatic failure.
D-galactosamine hydrochloride was used to induce pig model of fulminant hepatic failure, and the experiment animals were divided into model group (rapid injection of D-galactosamine hydrochloride by ear vein, a dose of 1.2 g/kg) and negative control group (5% Glucose). Clinical, biochemical and pathological changes of animals were observed. The expression of pigs fgl2 (pfgl2) mRNA in liver tissue was detected by real time RT-PCR, the expression of pfgl2 protein in liver tissue was detected by immunohistochemistry.
A pig model of fulminant hepatic failure was successfully established using the D-galactose hydrochloride; Real time RT-PCR of liver fgl2 mRNA showed that fgl2 mRNA expression was increased significantly in liver tissue of fulminant hepatic failure pig model compared with the control group (P = 0.016); Immunohistochemical staining showed that there were fgl2 protein expression in liver tissue of fulminant hepatic failure pig model, mainly in the membrane and cytoplasm of hepatocytes, inflammatory cells, liver sinusoidal endothelial cells and vascular endothelial cells of liver cell necrosis region. However, there are no fgl2 positive staining on negative control.
The pig model of fulminant hepatic failure induced by D-galactosamine hydrochloride is similar to human pathological process and can be used to evaluate the pre-clinical efficacy and safety of drug treatment on fulminant hepatic failure. Abnormal expression of pfgl2 at both mRNA level and protein level in the liver of fulminant hepatic failure pig model shows that pfgl2 induced coagulation pathway is also involved in the development of fulminant hepatic failure. Gene therapy targeting fgl2 genes for fulminant hepatic failure may provide a new means for the treatment of fulminant hepatic failure.
建立暴发性肝衰竭猪模型，用于评估药物治疗重症肝炎的临床前疗效，并检测该模型中纤维蛋白原样蛋白-2（fgl2）凝血酶原酶的表达，为暴发性肝衰竭的fgl2基因治疗提供依据。
采用盐酸D-半乳糖胺诱导猪暴发性肝衰竭模型，将实验动物分为模型组（经耳静脉快速注射盐酸D-半乳糖胺，剂量为1.2 g/kg）和阴性对照组（5%葡萄糖）。观察动物的临床、生化及病理变化。采用实时RT-PCR检测肝组织中猪fgl2（pfgl2）mRNA的表达，采用免疫组织化学法检测肝组织中pfgl蛋白的表达。
用盐酸D-半乳糖成功建立了猪暴发性肝衰竭模型；肝fgl2 mRNA的实时RT-PCR结果显示，与对照组相比，暴发性肝衰竭猪模型肝组织中fgl2 mRNA表达显著增加（P = 0.016）；免疫组织化学染色显示，暴发性肝衰竭猪模型肝组织中有fgl2蛋白表达，主要位于肝细胞、炎症细胞、肝窦内皮细胞及肝细胞坏死区血管内皮细胞的细胞膜和细胞质中。而阴性对照组无fgl2阳性染色。
盐酸D-半乳糖胺诱导的猪暴发性肝衰竭模型与人类病理过程相似，可用于评估药物治疗暴发性肝衰竭的临床前疗效和安全性。暴发性肝衰竭猪模型肝脏中pfgl2在mRNA和蛋白水平均异常表达，表明pfgl2诱导的凝血途径也参与了暴发性肝衰竭的发生发展。针对暴发性肝衰竭的fgl2基因治疗可能为暴发性肝衰竭的治疗提供新手段。
