肝郁气滞、肝胆湿热型胆囊胆固醇沉着症动物模型建立与评价  

Establishment and evaluation of animal model of gallbladder cholestasis

作　　者：王彤 张平 颜鑫园 蔡青原 陈建波 王雅蕾 刘文杰 朱豆豆 王旭[2] 谭琰[2] 李建军[1] 姚成礼[1] WANG Tong;ZHANG Ping;YAN Xinyuan;CAI Qingyuan;CHEN Jianbo;WANG Yalei;LIU Wenjie;ZHU Doudou;WANG Xu;TAN Yan;LI Jianjun;YAO Chengli(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院,北京100700 [2]北京中医药大学,北京100029

出　　处：《陕西中医》2024年第1期29-33,共5页Shaanxi Journal of Traditional Chinese Medicine

基　　金：首都卫生发展科研专项批准项目(首发2019-1-4097);北京市通州区科技计划项目(KJ2023CX062)。

摘　　要：目的:初步建立并评价肝郁气滞、肝胆湿热证型的胆囊胆固醇沉着症小鼠模型,为深入研究该病的发病机制、病理变化,探索临床治疗方案提供模型支持。方法:48只C57BL/6J雄性小鼠,随机分为空白对照组(WT)、造模3周组(LD-3)、造模6周组(LD-6)、造模9周组(LD-9),每组12只。WT组给予普通饲料+正常饮用水喂养,造模组分别给予3、6、9周高脂高胆固醇饲料+正常饮用水喂养。在造模期间,每日观察小鼠一般情况,分别在3、6、9周麻醉后处死动物,眼眶取血,检测血清中总胆固醇(TC)、甘油三酯(TG)含量,取组织标本,采用尼罗红染色观察胆囊脂质沉积情况,红外光谱分析胆汁成分;胆固醇代谢指标:免疫组化法检测肝脏三磷酸腺苷结合盒转运体A组1(ABCA1)蛋白表达,进行模型评价。结果:与WT组相比,各组造模小鼠体重显著增加(P<0.05);血清TC水平显著升高(P<0.05),血清TG水平明显降低(P<0.05);胆囊脂质沉积显著,胆汁混浊度增加;肝脏ABCA1蛋白表达明显增加。结论:本研究成功建立小鼠胆囊胆固醇沉着症模型构建方法,符合临床特征。并成功建立肝郁气滞、肝胆湿热证型的疾病证候类型,可为后续针对胆囊胆固醇沉着症发病机制及治疗方法研究提供稳定的动物模型。Objective:Establish and evaluate a mouse model of gallbladder cholesterol deposition with liver stagnation and qi stagnation,liver and gallbladder dampness heat syndrome,in order to provide model support for in-depth research on the pathogenesis,pathological changes,and exploration of clinical treatment plans of this disease.Methods:Overall,48 C57BL/6J male mice were randomly divided into a blank control group(WT),a 3-week modeling group(LD-3),a 6-week modeling group(LD-6),and a 9-week modeling group(LD-9),with 12 mice in each group.The WT group was fed with regular feed and normal drinking water,while the modeling group was fed with high fat and cholesterol feed and normal drinking water for 3,6,and 9 weeks,respectively.During the modeling period,the general situation of mice was observed daily.After 3,6,and 9 weeks of anesthesia,the animals were euthanized,and blood was collected from the orbit to detect the total cholesterol(TC)and triglyceride(TG)levels in serum.Tissue samples were taken to observe the lipid deposition in the gallbladder using Nile red staining,and bile components were analyzed using infrared spectroscopy.Cholesterol metabolism indicators:Immunohistochemical method was used to detect the protein expression of ATP binding cassette transporter A group 1(ABCA1)in the liver,and the model was evaluated.Results:Compared with the WT group,the weight of the model mice in each group increased significantly(P<0.05).The serum TC level significantly increased(P<0.05),while the serum TG level significantly decreased(P<0.05).Significant lipid deposition in the gallbladder and increased bile turbidity.The expression of ABCA1 protein in the liver was significantly increased.Conclusion:This study successfully established a mouse gallbladder cholesterol deposition model construction method using high fat and high cholesterol feed and normal drinking water for 9 weeks,which is in line with clinical characteristics.And successfully established the disease syndrome types of liver stagnation and qi stagnation,live

关 键 词：胆囊结石 胆囊息肉 高脂饮食 甘油三酯 动物模型 小鼠 

分 类 号：R575.6[医药卫生—消化系统]