肝性脑病动物模型的鉴定指标分析

Analysis of characteristic factors of hepatic encephalopathy in experimental rat model

目的:通过对慢性肝功能衰竭引起肝性脑病(hepat-ic encephalopathy,HE)发生模型的多指标观察和分析,寻找理想的HE模型的特征指标。方法:应用四氯化碳联合内毒素法制作慢性肝功能衰竭引起HE发生的模型,进行行为活动观察,血液生化、形态学、迷宫试验等检测。结果:模型组大鼠在造模过程中先后有67%(10/15)的动物死亡,出现呆滞、步态蹒跚、疼痛反应迟钝甚至消失等神经系统功能异常表现,并伴有血氨升高趋势,总胆红素、直接胆红素、γ-谷氨酰转肽酶升高(P<0.05),血浆蛋白、钙、钠和氯显著降低(P<0.01)。电镜检查显示模型组大鼠肝脏有纤维化性变化,海马脑片的神经元有趋向死亡性变化。完成造模的模型组大鼠与对照组相比,迷宫实验的测试结果没有显著性差异。结论:用四氯化碳联合内毒素法制作的慢性肝功能衰竭引起HE发生的模型,行为变化明确,但其他检测指标具有多样性和复杂性,需做进一步的综合性分析。

Objective ;To search an ideal characteristic factor for identifying experimental animal model of hepatic encephalopathy（HE） induced by chronic liver function failure in rats. Methods： In 15 male rats （model group）, carbon tetraehloride（CCl4） was injected is. c. , q. 3d. ） for 9 weeks, and then endotoxin（E, coli） was administrated（i, p. , q. d. ）for 2 days to induce chronic liver function failure resulting in HE, while 15 male rats were treated with saline as control group. The behavior activities were observed, and blood biochemistry, morphology of liver and brain by electron microscopy and maze experiment were tested. Results ： In model group, 67% of rats died during the course of model making, and in the meantime, abnormal appearances of nervous system function were observed including sluggishness, walking stagger, dullness even vanishing in nociceptive reaction. By comparing with control group, total bilirubin, direct bilirubin, and γ-glutamyl transpeptidase were increased （ P 〈 0.05） while plasma protein, Ca^2＋ , Na ^＋ and Cl^- were significantly decreased （ P 〈 0.01 ）. Blood ammonia increase （ P 〉 0.05） was only seen in model group. Moreover, ultrastructural examination by electron microscopy showed that the pathological changes of hepatic fibrosis in liver, the dying signs of neurons in hippocampus of rats in model group were observed. However, there was no significant difference in the maze test between model group and control group. Conclusion ： The animal model of hepatic encephalopathy resulted from chronic liver function failure may be made via CCl4 and endotoxin admin istration, identified by the monitoring of behavior activities. However, the other tested factors may be varied and complicated, and the charac teristic identification needs further investigation.