ConA与S-100分别诱导的自身免疫性肝炎动物模型的建立  

Establishment of two mouse models of autoimmune hepatitis induced by concanavalin A and S-100

作　　者：伍银银 许瑞蕊[1] 张洁[1] 周璐[1] 王邦茂[1] 

机构地区：[1]天津医科大学总医院消化内科,天津市300052

出　　处：《世界华人消化杂志》2014年第27期4113-4118,共6页World Chinese Journal of Digestology

摘　　要：目的:分别应用刀豆蛋白A(concanavalin A,ConA)及同种系肝抗原S-100建立自身免疫性肝炎(autoimmune hepatitis,AIH)的动物模型,并比较分析两种模型之间的异同.方法:向♀Balb/C鼠尾静脉注射ConA溶液,对照组注射生理盐水,分别于6、12、24及48 h取血及肝脏组织;向♀C57BL/6小鼠腹腔注射肝抗原S-100与等体积的弗氏完全佐剂(Freund's complete adjuvant,CFA)的乳化液,对照组注射生理盐水与CFA的混合物,4 wk后取血及肝脏组织.检测血清丙氨酸氨基转移酶(alanine transaminase,ALT),天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)水平,肝脏苏木素-伊红染液(HE)染色观察病理改变.结果:注射ConA后6 h ALT、AST水平均较正常对照组升高,肝脏出现轻度充血,少量淋巴细胞浸润,肝细胞轻度变性,12 h转氨酶升高达峰值(ALT:1603.40 U/L±461.24 U/L vs 66.25 U/L±18.66 U/L,P=0.000,AST:1877.20 U/L±623.23 U/L vs 159.50 U/L±29.22 U/L,P=0.000),24 h肝细胞变性、坏死增多,部分肝小叶结构消失,炎性细胞浸润增加.注射S-100后转氨酶水平较对照组显著增高(ALT:156.80 U/L±50.86 U/L vs 29.90 U/L±8.43 U/L,AST:317.80 U/L±105.80 U/L vs 146.40 U/L±30.61 U/L,P<0.01),肝脏细胞形态结构紊乱,局灶性细胞坏死伴肝小叶内大量炎细胞浸润.结论:两种模型均可作为AIH的动物模型,ConA模型呈急性病程,S-100模型呈慢性病程,可根据实验要求选择模型.AIM： To establish two autoimmune hepatitis （AIH） mouse models by injection of concanaval- in A （Con_A） and syngeneic S-100, respectively, and to compare the two models.METHODS： Female Balb/C mice received in- jection of ConA （15 mg/kg） through the tail vein, whereas control mice were injected with equal volume of sodium chloride. At 6, 12, 24 and 48 h after injection, blood and liver sam- ples were taken. In addition, female C57BL/6 mice were given syngeneic S-100 emulsified with equal volume of Freund＇s complete ad- juvant （CFA） by peritoneal injection at the Ist and 7th day, and the mixture of sodiumchloride and CFA were given to control mice. Blood and liver samples were taken 4 wk later. Serum levels of alanine transaminase （ALT） and aspartate aminotransferase （AST） were tested using an automatic biochemistry analyzer. Liver pathological changes were observed after hematoxylin and eosin （HE） staining.RESULTS： Serum levels of ALT and AST in- creased significantly 6 h after ConA injection and reached the peak at 12 h in comparison with the control group. The peak values of ALT and AST were significantly higher than those in the control group （ALT： 1603.40 U/L ± 461.24 U/L vs 66.25 U/L ± 18.66 U/L, AST： 1877.20 U/L ± 623.23 U/L vs 159.50 U/L ± 29.22 U/L, P 〈 0.01）. Liver tissue showed mild congestion, infiltration of few inflammatory cells and hepatocyte degeneration 6 h after ConA injection. Degeneration and necrosis of hepatocytes and inflammatory cell infiltra- tion became more significant and part of liver lobules disappeared at 24 h. Serum levels of ALT and AST in mice injected with syngeneic S-100 were significantly higher than those in the controls （ALT： 156.80 U/L ± 52.86 U/L vs 29.90 U/L ± 8.43 U/L; AST： 317.80 U/L ± 105.80 U/L vs 146.40 U/L ± 30.61 U/L, P 〈 0.01）. The liver cells were arranged irregular- ly, and local necrosis and massive inflamma- tory cell infiltration were observed in model mice.CONCLUSION： Animal models created with

关 键 词：自身免疫性肝炎 刀豆蛋白A S-100 BALB/C小鼠 C57BL/6小鼠 

分 类 号：R575.1[医药卫生—消化系统]