应用四环素灌胃建立小鼠急性肝损伤模型的初步研究  

Preliminary study on the establishment of mouse model of acute liver injury by perfusing stomach with tetracycline

作　　者：禄保平[1] 杨晓娜[1] 许家艳[1] 

机构地区：[1]河南中医学院肝病研究所,河南郑州450008

出　　处：《南京医科大学学报（自然科学版）》2006年第8期671-675,F0006,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：河南省科技攻关项目(0324410026)

摘　　要：目的:探索应用四环素灌胃建立小鼠急性肝损伤模型,并初步阐明其发生机制。方法:先以不同剂量四环素灌胃,18h后检测小鼠血清ALT、AST水平并进行光镜观察,探索导致明显急性肝损伤的相对合适剂量;再以相对合适剂量四环素灌胃,18、36、54、72h后分别检测小鼠血清ALT、SOD、MDA、GSH-PX、IL-18水平及肝细胞凋亡情况,并进行光镜、电镜观察,探索导致明显急性肝损伤的相对合适时间及可能机制。结果:10倍和15倍剂量时,小鼠血清ALT、AST明显升高,肝细胞出现明显病理改变;应用10倍剂量四环素灌胃18h后,小鼠血清ALT和IL-18水平明显升高,肝细胞广泛损伤,细胞超微结构显著变化,肝细胞凋亡程度严重。结论:应用10倍剂量四环素灌胃18h可成功造成小鼠急性肝损伤模型,其发生与IL-18水平升高和肝细胞凋亡密切相关。Objective： To explore the method of establishing mouse model of acute liver injury by perfusing stomach with tetracycline, and to illuminate the mechanism. Methods： Experimental mice were perfused with different dosages of tetracycline. Eighteen hours later, the serum levels of ALT, AST were measured and the liver tissues were observed by photics microscope to find the relative suitable dosage that can obviously induce acute liver injury.Then the suitable dosage was given in the same way ,and the levels of ALT,SOD,MDA,GSH-PX,IL-18 in serum were measured 18,36,54,72 h later respectively. The condition of cell apoptosis was analyzed,and the tissues were observed by photics microscope and electron microscope to find the relative suitable time. Results： At the dosages of 10 and 15 times,the serum levels of ALT and AST of the experimental mice were obviously higher and the liver cells appeared visible pathological changes. 18 hours after the treatment of using 10 times dosage,the levels of ALT and IL-8 in serum were significantly increased and the liver cells were impaired,and the degree of the liver cell apoptosis was serious. Conclusion： Mouse model of acute liver injury can be successfully established by perfusing stomach with tetracycline at 10 time dosage for 18 hours. The mechanism is closely related to the increase of IL-8 level and the liver cell apoptosis.

关 键 词：急性肝损伤 动物模型 四环素 IL-18 细胞凋亡 

分 类 号：R575.29[医药卫生—消化系统]