建立适合MRI检查鼠肝纤维化、肝硬化模型的可行性研究  

Feasibility study on liver fibrosis and cirrhosis rat model for MRI detection

作　　者：孟令平[1] 王国光 胡明秀[1] 洪玉萍[2] 官兵[2] 乔伟伟[3] 

机构地区：[1]上海市第六人民医院金山分院放射科,上海201500 [2]上海市第六人民医院金山分院病理科,上海201500 [3]复旦大学动物科学实验部,上海200232

出　　处：《生物医学工程与临床》2015年第5期443-448,共6页Biomedical Engineering and Clinical Medicine

基　　金：上海市科委医学引导类项目(12119b1400)

摘　　要：目的 探讨硫代乙酰胺（TAA）诱导大鼠肝纤维化及肝硬化模型符合MRI影像学研究的可行性。方法 清洁级SD大鼠100只，雄性，鼠龄6 ～ 7周，体质量180 ～ 200 g。随机分为实验组（n = 84）、对照组（n = 16）2组。实验组采用TAA腹腔定点注射，剂量200 ～ 240 mg/kg，3次/周。对照组同期腹腔注射同剂量的0.9 %氯化钠溶液。建模后第6 ～ 30周末分批（1 ～ 5只/批次）做MRI检查，活体左心室抽血2 mL做实验室检查；病理组织将肝损伤分为肝纤维化Ⅰ ～ Ⅳ期、肝硬化小结节期、肝硬化大结节期，并与血清学指标对照。结果 对照组大鼠肝脏质地柔软光滑，色泽均匀暗红。实验组第6 ～ 14周末发生肺水肿10只；第6 ～ 22周末发展为肝纤维化期39只；第23 ～ 30周末演变为肝硬化结节期30只，多数肝结节能够在MRI影像显示，T1加权成像（T1WI）呈等、高信号，T2加权成像（T2WI）呈等、稍低信号，肝轮廓不规整；增强扫描肝结节大多与肝实质同步强化。肝碱性磷酸酶（ALP）、总胆汁酸（TBA）、AST（天冬氨酸转氨酶）、丙氨酸氨基转移酶（ALT）及透明质酸（HA）、Ⅲ型前胶原肽（PⅢNP）、层粘连蛋白（LN）、Ⅳ型胶原（CⅣ）血清含量在肝纤维化早期即升高，随着建模时间延长逐渐增加，肝硬化大结节期血清指标略有下降。与对照组比较，实验组不同阶段肝纤维化、肝硬化期血清ALP、TBA、AST、ALT及HA、PⅢNP、LN、CⅣ含量均有统计学意义（P 〈 0.05）。结论 TAA诱导的大鼠肝纤维化及肝硬化模型，较为适合MR不同序列的影像学研究。Objective To investigate the feasibility of establishing thioacetamide （TAA） induced rat liver fibrosis and cirrhosis model suitable for MRI image study. Methods A total of 100 male SD rats of clean grade were collected, aged 6 - 7 weeks with body weight 180 - 220 g. The animals were randomly divided into experimental group （n = 84） and control group （n = 16）. Rats in experimental group were given TAA intraperitoneal injection with 200 mg/kg at 3 times/week, while rats in control group were given 1 mL 0.9 % sodium chloride solution injection into abdominal cavity, and all rats were under conventional feeding for 30 weeks. At 6 - 30 weeks of modeling, the rats were performed MRI in batches （1 - 5/batch）, and 2 mL living blood from left ventricular was draw for laboratory tests. The pathologic liver damage were divided into liver fibrosis Ⅰ - Ⅳ stage, cirrhosis small nodules（1 - 3 mm）, cirrhosis large nodules （diameter 〉 3 mm） and compared with serological index. Results Liver surface of control group rats was soft and smooth with even dark red. At 6 - 14 weeks, experimental pulmonary edema complications occurred in 10 rats. At 6 - 22 weeks, 39 rats were developed of liver fibrosis stage, while 30 rats for cirrhotic nodules at 23 - 30 weeks. The majority of liver nodules were shown in MRI, with T1WI showed as iso-intense or slight hyper-intense signal, T：WI as iso-intense or slight hypo-intense signal, and liver contour irregular. Enhanced scanning image showed that cirrhotic nodule synchronously enhanced with normal parenchyma liver. The alkaline phosphatase （ALP）, total bile acid （TBA）, aspertate aminotransferase （AST）, alanine aminotransferase （ALT）, hyaluronic acid （HA）, proeollagen Ⅲ N-terminal peptide （PⅢ NP）, laminin （LN） and collagen type Ⅳ （C Ⅳ ） serum levels increased slightly in early stage of liver fibrosis, while the liver cirrhosis phase index reduce slightly along with time increasing after modeling. Compared with control group,

关 键 词：硫代乙酰胺 肝纤维化 肝硬化 大鼠模型 MRI 病理学 血清学 

分 类 号：R445.2[医药卫生—影像医学与核医学] R575.2[医药卫生—诊断学]