以环孢素灌胃建立急性肝损伤小鼠模型的初步研究  

PRIMARY STUDY ON THE ESTABLISHMENT OF MOUSE MODEL OF ACUTE LIVER INJURY BY PERFUSING STOMACH WITH CICLOSPORIN A

作　　者：禄保平[1] 杨晓娜[1] 巴明玉[1] 

机构地区：[1]河南中医学院肝病研究所,郑州450008

出　　处：《现代预防医学》2010年第17期3313-3315,3323,共4页Modern Preventive Medicine

基　　金：河南省科技攻关项目(0324410026);河南省高等学校青年骨干教师资助计划项目(教高[2007]335号)

摘　　要：[目的]探索以环孢素(CsA)灌胃建立急性肝损伤小鼠模型,并初步阐明其发生机制。[方法]先以不同剂量CsA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(10倍)CsA灌胃,18、36、54、72h后分别检测小鼠血清ALT并进行光镜观察,探索导致明显急性肝损伤的相对合适时间;然后以10倍剂量CsA灌胃,经相对合适时间(18h)后分别检测小鼠血清ALT、AST、SOD、MDA、GSH-Px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;10倍剂量CsA灌胃18h后,小鼠血清ALT、AST、MDA水平明显升高,SOD、GSH-Px水平明显降低,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CsA灌胃18h可成功造成小鼠急性肝损伤模型,其发生与自由基脂质过氧化反应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 Ciclosporin A （ CsA） , and to illuminate its mechanism. [ Methods] Experimental mice were perfused with different dosages of CsA. 18 hours later, the serum levels of ALT, AST were measured and the liver tissues were observed by photics microscope to find a relative suitable dosage that could obviously induce acute liver injury. Then the suitable dosage （10 times） CsA was given in the same way, and the levels of ALT in serum were measured 18, 36, 54, 72h later respectively, and the tissues were observed by photics microscope to find a relative suitable time. Finally, 10 times dosage CsA was given, and the levels of ALT, AST, SOD, MDA and GSH-Px in serum were measured respectively after the relative suitable time （18h）. The condition of cell apoptosis was analyzed, and the tissues were observed by photics microscope and electron microscope to explore its underlying mechanism. [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 perfusion with 10 times dosage of CsA into the stomach, the levels of ALT, AST and MDA in serum were significantly increased, while the levels of SOD and GSH-Px were significantly lower, and the liver cells were impaired widely, the ultramicrostructure of which obviously changed, and the degree of the liver cell apoptosis was serious. [Conclusion] Mouse model of acute liver injury can be successively established by perfusing stomach with CsA at 10 times dosage for 18 hours. Its mechanism may be closely related to lipid peroxidation of free radical and the liver cell apoptosis.

关 键 词：肝脏疾病 模型 动物 环孢素 脂质过氧化作用 细胞凋亡 

分 类 号：R-332[医药卫生]