实验性大鼠恶性胸膜间皮瘤动物模型的建立及影像检查的意义

Establishment of an induced rat model of malignant pleural mesothelioma

目的 建立一种简便、实用、诱发率高、较接近人体恶性胸膜间皮瘤 (MPM )的动物模型 ,进行影像和病理的研究及对照。方法 Wistar大鼠 10 0只 ,右侧胸膜腔闭式染尘法注入石棉纤维混悬液 4 0mg ,对照组 2 0只 ,注入等量灭菌生理盐水。每隔 1～ 3个月对实验组 10～ 30只 ,对照组 3～ 5只大鼠胸部CT扫描 ,动态观察MPM的发生情况 ,不处死大鼠而待其自然死亡 ,死亡鼠先行CT扫描后再做病理学检查 ,整个实验周期历时 2年。结果 对照组中无自发性MPM。实验组有效动物为 95只 ,其中有MPM 6 8只 ,诱发率 71 6 %。 6 8只中胸膜不典型增生 13只 ,胸膜阴性 14只。病理表现分为结节型、斑片型和巨块型 ;组织学分为纤维型、上皮型和混合型。 3～ 8个月内CT扫描胸膜无异常 ,9～ 2 4个月开始出现MPM的多种形式改变 ,如胸膜增厚 ,增厚胸膜密度不均匀 ;肿块 ;纵隔增宽 ;纵隔胸膜改变 ;邻近组织 (心包、心脏、膈肌、胸、肺 )的浸润及远距离的转移等较特征性的MPM征象。其中结节状胸膜增厚仅发生在MPM ,最早发生在 2 5 0d。结论 该模型与临床有较好的对应性 ,弥补了临床上很难获得新鲜、不同肿瘤时期肿瘤组织标本的缺陷 ;不同时期CT检查有阶段性改变和特征性的征象。可用于影像学等多种研究 。

Objective To establish a convenient and practical malignant pleural mesothelioma (MPM) model induced by crocidolite in Da Yao, which has a high induction rate and can be used for imaging and multiple experimental studies and is similar to human MPM .Methods 40 mg of crocidolite suspension was injected into the right chest cavity in 100 Wistar rats in the test group, while same amount of sterilized saline water was injected in 20 rats in the control group. The animals were observed daily, and weighted once a month. CT scanning was performed regularly. When the rats were dead or dying, they were dissected immediately and pathological changes were recorded after CT examination. The experiment lasted for 2 years.Results The overall induction rate was 71.6%. The survival time of the first MPM rat was (285 days.) The mean living span of rats with MPM was (469±21) days. The pathological features of the induced MPMs were multiple morphologically and there were some CT features in different periods. CT imaging could show some MPM features and find the tumour earlier. Conclusion The cause, positions, tissues and clinical condition of induced tumors were the same as humans. The model had a higher similarity with human MPM in differentiation degree and histological type, and the model can be used to study the mechanism of MPM, to discuss the measures of prevention, and to guide clinical diagnosis and treatment. Multi-morphology of the history from the induced tumors could make up the shortage, which was the difficulty in getting all periods of tissue samples in clinical research and being used in imaging and many kinds of researches. It was a valuable animal model to study MPM.