李鑫 王权 陈思源 张逢 余曦明

摘要：目的 通过构建肝纤维化大鼠肝郁病证结合的模型，为相关研究提供模型参考依据和临床治疗提供诊疗思路。方法 将30只SD大鼠随机分成2组，即空白组和模型组，每组15只。模型组大鼠每天定期皮下注射四氯化碳（carbon tetrachloride，CCL4）+ 橄榄油，自第5周起每日加用夹尾进行刺激，每次30min，3次/天;空白组大鼠每天定期皮下注射橄榄油，2组均连续给药8周。实验结束后记录动物和肝脏重量，收集肝脏组织制作石蜡切片染色后观察其病理变化，用ELISA法检测血清中AST和ALT相关活力指标。结果 （1）与空白组比较，模型组肝脏重量明显增加（P<0.05），血清中AST和ALT的活力显著升高（P<0.05或P<0.01）。（2）形态学结果显示：模型组大鼠肝脏出现了典型的肝纤维化病理改变，主要表现为肝组织内纤维结缔组织增生，脂肪空泡形成及相关炎性细胞浸润等。结论 采用此种方法造模可升高大鼠血清的AST和ALT活力，肝脏呈纤维化改变，成功建立了肝纤维化大鼠模型，是较为理想的造模方法。

关键词：肝纤维化;大鼠;模型;肝功能

中图分类号：R575 文献标志码：B 文章编号：1007-2349（2021）06-0066-04

【Abstract】Objective： To provide a model reference basis and clinical treatment ideas for related research by constructing a model combining liver depression and syndromes in rats with liver fibrosis. Methods： 30 SD rats were randomly divided into 2 groups， namely the blank group and the model group， 15 rats per group. The rats in the model group were given regular subcutaneous injections of carbon tetrachloride （CCL4） + olive oil every day， and starting from the 5th week， the tail clamp was added every day for stimulation， 30 minutes each time， 3 times a day. The rats in the blank group were given subcutaneous injection of olive oil every day. Both groups were given continuous administration for 8 weeks. After the experiment， the weight of the animals and liver was recorded. The liver tissues were collected to make paraffin sections and stained to observe the pathological changes. ELISA method was used to detect the AST and ALT related vitality indicators in the serum. Results： （1） Compared with that of the blank group， the liver weight of the model group was significantly increased （P<0.05）， and the activity of AST and ALT in the serum was significantly increased （P<0.05 or P<0.01）. （2） The morphological results showed that the liver of the model group showed typical pathological changes of liver fibrosis， which were mainly manifested as the hyperplasia of fibrous connective tissue in the liver tissue， the formation of fatty vacuoles and the infiltration of related inflammatory cells. Conclusion： Modeling with this method can increase the activity of AST and ALT in rat serum， and the liver shows fibrotic changes. The successful establishment of a rat model of liver fibrosis is an ideal method for modeling.

【Key words】Liver fibrosis; Rat; Model; Liver Function

肝纖维化（1iver fibrosis，LF）是对各种慢性肝脏损伤的一种代偿性反应，是“慢性肝炎-肝纤维化-肝硬化”发展的中心环节。目前，肝纤维化的形成被认为是一个动态的过程，涉及复杂的细胞和分子机制，导致组织修复机制的慢性激活。如果慢性损伤持续存在，炎症和纤维化可能发展成肝硬化，最终导致器官衰竭和死亡[1]。由此可见，肝纤维化是绝大多数慢性肝病的共同病理基础，同时也是多种慢性肝病向肝硬化发展的共同病理组织学基础。各种肝病多数经肝纤维化最后发展为晚期的肝硬化成为肝病死亡的主要原因。肝纤维化是严重威胁人类健康的疾病之一，但到目前为止，关于肝纤维化的治疗方面，暂无理想的治疗方法与治疗策略，抗肝纤维化治疗成了目前世界级医学难题。……