小型猪肝硬化模型肝脏病理及生化指标的变化

Pathological and biochemical changes of the liver in mini-pig models of hepatic cirrhosis

目的探讨小型猪肝硬化模型制备过程中肝脏病理学及生化指标的变化。方法选用同种系巴马小型猪50头,随机分为实验组40头,对照组10头,雌雄不限,4月龄,体重15～20 kg。实验组予四氯化碳复合因素造模法喂养,正常组予饲料及清水喂养。于造模的0、4、8、12、16、20、24周末进行肝脏穿刺活检及耳缘静脉抽血进行数据采集,对比分析肝纤维化-肝硬化制模过程中的肝脏病理学及生化指标的变化。结果 24周末,对照组获得数据S0期70例次;实验组获得数据轻度肝纤维化(S1+S2期)82例次,重度肝纤维化(S3+S4期)62例次,肝硬化共39例次。从正常组到肝硬化组丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素、血清肌酐及球蛋白呈逐渐升高的趋势,而白蛋白,A/G比值呈逐渐下降的趋势,凝血酶原时间则逐渐延长,统计学分析,组间存在明显差异(P<0.01)。结论四氯化碳复合因素造模法可以成功制备出小型猪肝硬化模型,肝纤维化不同阶段肝脏病理学和生化指标均发生明显变化。

Objective To assess the pathological and biochemical changes of the liver during the establishment of mini-pig models of hepatic cirrhosis. Methods Fifty Bama mini-pigs of the same germline, male or female, aged 4 months, weighing 15 ~ 20 kg, were included in this study. The mini-pigs were divided at random into an experimental group of 40 and a control group of 10 animals. Compound feed including carbon tetrachloride and phenobarbitone was employed to establish the mini-pig models in the experimental group, and normal feed was given to the control mini-pigs. Liver puncture biopsy was performed and the blood samples were taken from the ear vein at the end of 0＇h , 4th, 8＇h, 12＇h, 16＇h, 20＇~, 24thweeks for pathological and biochemical examinations, respectively. Results At the end of 24＇hweek, there were 70 stage 0 hepatic fibrosis in the normal group, while in the experiment group there were 82 slight hepatic fibrosis （ stage SI ＋ S2）, 62 severe hepatic fibrosis （ stage S3 ＋ S4）, and 33 hepatic cirrhosis. From the normal to cirrhosis, the ALT, AST, T. BIL, CR and GLO were gradually elevated, ALB gradually decreased, A/G ratio inversed, and PT was gradually prolonged, with statistically significant differences between the different lesion groups （P 〈 0.01 ）. Conclusions Compound feed including carbon tetrachloride and phenobarbitone can be used to successfully establish mini-pig models ofhepatic cirrhosis, showing significant changes of liver pathology and biochemistry at different stages of the development of hepatic fibrosis.