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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 m L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MRI不同序列的影像学研究。
Objective To investigate the feasibility of thioacetamide (TAA) -induced liver fibrosis and cirrhosis in MRI imaging studies. Methods One hundred male SD rats of clean grade were aged 6-7 weeks with a body weight of 180-200 g. Randomly divided into experimental group (n = 84), control group (n = 16) 2 groups. Experimental group using TAA peritoneal fixed-point injection, the dose of 200 ~ 240 mg / kg, 3 times / week. In the control group, the same dose of 0.9% sodium chloride solution was injected intraperitoneally. MRI was performed in batches (1-5 batches / batch) from the 6th to the 30th week after modeling, and the left ventricular blood was drawn for 2ml in the laboratory for laboratory examination. The pathological tissues were divided into liver fibrosis Ⅰ ~ Ⅳ , Cirrhosis nodules, cirrhosis large nodules, and with serum markers. Results The liver of rats in the control group was soft, smooth and dark red in color. In the experimental group, 10 pulmonary edema occurred at the 6th to the 14th week in the experimental group; 39 cases developed liver fibrosis from the 6th to the 22nd week; 30th liver cirrhosis was observed on the 23rd to 30th week. The results showed that T1WI was equal and high signal, T2WI was equal and slightly lower signal, and the hepatic outline was irregular. Most of enhanced hepatic nodules were enhanced synchronously with the liver parenchyma. ALP, TBA, AST, ALT and HA, PⅢNP, , Laminin (LN) and collagen Ⅳ (CⅣ) increased in the early stage of hepatic fibrosis, and gradually increased with the extension of modeling time. The serum indexes of cirrhosis with a large nodule decreased slightly. Compared with the control group, the levels of serum ALP, TBA, AST, ALT, HA, PⅢNP, LN and CⅣ in liver fibrosis and cirrhosis were significantly different in the experimental group (P <0.05). Conclusion TAA-induced rat liver fibrosis and cirrhosis models are more suitable for imaging studies of different sequences of MRI.