四氯化碳诱导肝硬化动物模型的相关影响因素  

Influencing factors in the establishment of the rat model of liver cirrhosis with carbon tetrachloride

作　　者：崔承虎 金世柱[1] 韩明子[1] 李瑞妮[1] 荣为为 孙爆冷 

机构地区：[1]哈尔滨医科大学第二附属医院消化内科,哈尔滨医学硕士150081

出　　处：《医学研究生学报》2015年第9期910-914,共5页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81370557)

摘　　要：目的四氯化碳(CCl4)模型中有多种因素影响建模效果,如药物浓度、给药方式等,但关于评价建模效果的研究尚少。文中探索CCl4不同给药途径、药物浓度及给药时间与大鼠肝硬化建模效果之间的关系。方法实验用CCl4诱导大鼠肝硬化,分别有给药途径、药物浓度、给药时间3个因素,其中给药途径因素包括皮下注射、腹腔注射、灌胃等3个水平,药物浓度因素包括30%、50%2个水平,给药时间因素包括8、10、12周等3个水平,共计18个处理组。各组动物按各自不同的途径和浓度给药,以30%乙醇为唯一饮料,在预订时间检查各项化验指标和组织形态学变化,采用大鼠肝硬化疾病评分模型(scoring model for liver cirrhosis disease,SLCD)和拉埃内克纤维化评分系统(Laennec fibrosis scoring system,LFSS)测得生化和组织形态学分值,分别以R值和L值表示,结果用析因设计实验(3×2×3),对各因素的各水平全部组合进行实验。结果腹腔注射组R值<皮下注射组和灌胃组,50%CCl4油剂组R值<30%CCl4油剂组,随着给药时间的延长R值呈降低趋势,析因方差分析结果显示3种因素主效应均有统计学意义(P<0.05),给药方式与给药时间、药物浓度之间有相互关系(P<0.05)。LFSS析因分析结果表明腹腔注射组L值>皮下注射组、灌胃组,50%CCL4油剂组L值>30%CCl4油剂组,12周组L值>10周组>8周组,析因方差分析结果显示3种因素主效应均有统计学意义(P<0.05),给药方式和给药时间及给药方式和药物浓度组之间无相互关系(P>0.05)。30%、50%CCl4腹腔注射、皮下注射、灌胃组的死亡率依次升高(分别为25.33%、37.78%、38.37%和42.97%、47.85%、51.88%),50%CCl4组死亡率高于30%CCl4组。但经log-rank检验比较各组生存曲线,不同给药方式组及药物浓度组之间差异并无统计学意义(P>0.05)。结论腹腔注射给药肝硬化模型效果优于皮下注射和灌胃方法。3种给药方法都随药物浓度及�Objective Liver cirrhosis modeling with carbon tetrachloride （CCL4） may be influenced by many factors, such as drug concentration and dosing methods. In this article, we explored the influences of different concentrations and different dosing methods and time of CCL4 on the induction of liver cirrhosis in rats. Methods We constructed rat models of liver cirrhosis with different concentrations of CCL4 （30% and 50% ）, using different dosing methods （subcutaneous injection, intraperitoneal injection, and intragastric administration）, and for different lengths of dosing time （8 wk, 10 wk, and 12 wk）. We collected blood and liver tissues from the rats at different time points for HE and MTC staining, biochemical and histomorphological scores based on the Scoring Model for Liver Cirrhosis Disease （SLCD, expressed by R） and the Laennec Fibrosis Scoring System （LFSS, expressed by L）, and analysis of the results by 3 × 2 ×3 factorial experiment design. Results The R value was lower in the intraperitoneal injection than in the subcutaneous injection and intragastric administration groups, and so was it in the 50% than in the 30% CCL4 group, decreasing with the extending of dosing time, with statistically significant differences in the main effects （ P 〈 0.05 ） as well as a remarkable correlation among drug concentrations, dosing methods, and dosing time （P 〈 0. 05）. The L value was higher in the intraperitoneal injection than in the subcutaneous injection and intragastric administration groups, and so was it in the 50% than in the 30% CCL4 group and in the 12 wk than in the 10 wk and 8 wk groups, with statistically significant differences in the main effects （ P 〈 0.05 ） but no remarkable correlation among drug concentrations, dosing methods, and dosing time （P 〉 0.05）. The death rate showed an increasing trend in the intraperitoneal injection, subcutaneous injection and intragastric administration of 30% CCL4 （25.33%, 37.78%, and 38.37% ） and 50% CCL4 （42.97%, 47.85%

关 键 词：四氯化碳 肝硬化 动物模型 影响因素 

分 类 号：R575[医药卫生—消化系统]