两种不同种属小鼠急性免疫性肝损伤模型的比较  

Comparison of acute immunological liver injury models in two different species of mice

作　　者：胡宁 黄涵年[2] 夏道宗[1] HU Ning;HUANG Hannian;XIA Daozong(College of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053;College of Applied Engineering,Zhejiang Institute of Economics and Trade,Hangzhou 310018,China)

机构地区：[1]浙江中医药大学药学院,浙江杭州310053 [2]浙江经贸职业技术学院应用工程学院,浙江杭州310018

出　　处：《基础医学与临床》2023年第9期1364-1368,共5页Basic and Clinical Medicine

基　　金：浙江经贸职业技术学院省属高校基本科研业务费专项资金(20YQ07);浙江省教育厅一般科研项目(Y202146604)。

摘　　要：目的探讨刀豆蛋白A(ConA)引起两种不同种属小鼠急性免疫性肝损伤的剂量差异。方法雄性BALB/C小鼠和雄性C57BL/6小鼠分别为36只和40只。BALB/C小鼠分为对照组和5个(5、10、15、20和25 mg/kg ConA)实验组,C57BL/6小鼠分为对照组和5个(5、7.5、10、12.5和15 mg/kg ConA)实验组,实验组尾静脉注射设定剂量ConA。禁食不禁水,16 h后摘眼球采血,并取肝、脾和胸腺组织称重计算脏器指数,病理学检测肝组织,比色法测定血清中天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)活性,ELISA检测血清中肿瘤坏死因子α(TNF-α)含量,并结合各组动物死亡率,以确定最佳ConA剂量。结果在BALB/C小鼠中,25 mg/kg剂量ConA死亡2只;AST、ALT活性和TNF-α含量与ConA呈剂量依赖性升高(P<0.05);肝脏指数与ConA的剂量呈现正相关(P<0.05);脾脏指数在5 mg/kg时高于10和15 mg/kg,表现出先升高再降低再升高的趋势。在C57BL/6小鼠中,ConA剂量在10、12.5和15 mg/kg时分别死亡1只、1只和2只;AST、ALT活性和TNF-α含量与ConA也呈剂量依赖性升高(P<0.05);肝脏指数与ConA的剂量呈正相关(P<0.001);脾脏指数在7.5 mg/kg时高于其余剂量组,总体表现为先升高后降低的趋势。在两个品系的小鼠中,胸腺指数均随着剂量的升高而降低。两种小鼠肝脏病变程度与ConA剂量呈正相关,从低剂量时的炎性细胞浸润发展为高剂量时的肝细胞坏死,从灶状坏死发展为片状坏死。结论C57BL/6小鼠较BALB/C小鼠对ConA敏感性更高,BALB/C小鼠复制动物模型的合适剂量为20 mg/kg,而C57BL/6小鼠复制动物模型的合适剂量为10 mg/kg。Objective To explore the dose difference on concanavalin A(Con A)induced acute immunological injury of liver in two different species of mice.Methods Thirty six male BALB/C mice and 40 male C57BL/6 mice were randomly divided into 6 groups.BALB/C mice were divided into a control group and five(5,10,15,20 and 25 mg/kg ConA)experimental groups,while C57BL/6 mice were divided into a control group and five(5,7.5,10,12.5 and 15 mg/kg ConA)experimental groups.The experimental groups were injected with different doses of ConA.After 16 hrs of fasting,the serum samples were collected by orbital blood sampling.Biopsy samples of liver,spleen andthymus were weighed and visceral index was calculated.The liver tissue was microscopied with histological technology.The activity of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)was measured by colorimetric method.The release and expression of tumor necrosis factor(TNF-α)were detected using ELISA.Finally,the ConA optimum dose was determined based on animal mortality in each group.Results In BALB/C mice,two animals died at the dosage of 25 mg/kg ConA.The activity of AST,ALT and TNF-αcontent showed a dose-dependent increase with ConA(P<0.05).The liver index was positively correlated with the dose of ConA(P<0.05).The spleen index from group of 5 mg/kg was higher than that from groups of 10 and 15 mg/kg,showing a tend of increase-decrease-increase kinetic profile.In C57BL/6 mice,one animal died at the dosage of 10 mg/kg ConA,one at 12.5 mg/kg and two at 15 mg/kg ConA.The activity of AST,ALT and TNF-αcontent showed a dose-dependent increase with ConA(P<0.05).The liver index was positively correlated with the dose of ConA.The spleen index at 7.5 mg/kg was higher than other dose groups,showing a trend of increase followed by decrease.In both strains of mice,thymus index decreased with the increase of dose.The extent of liver lesions in both species of mice was positively correlated with the dose of ConA,progressing from inflammatory cell infiltrates at low doses to live

关 键 词：刀豆蛋白A 免疫性肝损伤 模型小鼠 

分 类 号：R392.9[医药卫生—免疫学]