家兔肝纤维化模型四氯化碳剂量递增法

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目的建立家兔纤维化模型并探讨其发生发展过程中生化指标及病理形态学动态变化。方法 35只雄兔,随机分为对照组(n=7)和模型组(n=28),模型组家兔皮下注射40%四氯化碳(CCl4)建立肝纤维化模型,按剂量递增方法,即前2周0.2 mL/kg,在第3、9及15周,剂量分别增至0.5、1.0、1.5 mL/kg,每周2次,连续2周停药1周,连续处理20周,分别在第0、5、8、11、17、20周末进行病理学及血清生化指标检测。结果实验过程中,模型组家兔死亡2只;随着造模时间延长,肝细胞脂肪变性、坏死逐渐形成纤维间隔,肝小叶结构紊乱,最终形成假小叶,第8、11、17、20周纤维化评分分别为(1.4±0.54)、(1.8±0.45)、(2.8±0.45)、(3.57±0.55)分,明显高于对照组(P<0.05);模型组家兔血清谷丙转氨酶、谷草转氨酶呈一过性升高趋势,在造模第8周分别增至(355.1±311.5)、(840.5±45.8)U/L,明显高于对照组(P<0.01),随后逐渐减弱。结论 CCl4皮下注射20周可成功建立稳定的家兔肝纤维化模型,且死亡率较低,是一种较为理想的实验性肝纤维化模型制备方法。 OBJECTIVE: To establish a rabbit model of fibrosis and to investigate the biochemical parameters and pathomorphological changes in the process of its development. Methods 35 male rabbits were randomly divided into control group (n = 7) and model group (n = 28). The model group was subcutaneously injected with 40% carbon tetrachloride (CCl4) to establish the hepatic fibrosis model. Namely 0.2 mL / kg in the first 2 weeks and doses 0.5, 1.0 and 1.5 mL / kg in the 3rd, 9th and 15th week, respectively, twice a week for 1 week for 2 weeks and continuous treatment for 20 weeks respectively At 0, 5, 8, 11, 17 and 20 weeks, pathological and serum biochemical indexes were detected. Results During the experiment, there were 2 rabbits died in model group. With the prolongation of modeling time, fatty degeneration and necrosis of hepatocytes gradually formed fibrous septum and hepatic lobule structure disorder, finally forming pseudolobules. At the 8th, 11th, 17th and 20th weeks (1.4 ± 0.54), (1.8 ± 0.45), (2.8 ± 0.45) and (3.57 ± 0.55) respectively, which were significantly higher than those in the control group (P <0.05). Serum alanine aminotransferase, The aspartate aminotransferase (AST) increased transiently to (355.1 ± 311.5) and (840.5 ± 45.8) U / L in the 8th week of modeling, which was significantly higher than that of the control group (P <0.01), and then gradually weakened. Conclusion CCl4 can establish a stable model of hepatic fibrosis in rabbits 20 weeks after subcutaneous injection, and its mortality rate is relatively low. It is an ideal experimental method for preparing hepatic fibrosis model.
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