紫杉醇所致SD大鼠外周神经病变模型的建立

目的 化疗药物所致的外周神经病变（chemotherapy-induced peripheral neuropathy,CIPN）是多种化疗药物的共同而严重的不良反应.目前,国内外最常用的CIPN模型是紫杉醇（PTX）腹腔注射建立的SD大鼠模型,但关于影响CIPN模型建立的相关因素却少有涉及.本实验拟考察影响PTX所致SD大鼠CIPN模型的影响因素,为筛选和研究防治CIPN药物提供理想的动物模型.方法 大鼠隔日一次腹腔注射给予PTX,采用测痛丝致痛行为学实验考察PTX对大鼠机械性异常性疼痛和机械性痛觉过敏的影响,免疫荧光法检测大鼠后足表皮下神经纤维（intraepidermal nerve fiber,IENF）的形态及数目,电子显微镜检测坐骨神经细胞线粒体的形态及数目.结果 隔日腹腔注射2 mg/kgPTX四次对SD大鼠的体重增长无明显影响；给予PTX后,初始体重为200 g的大鼠在34 d的实验周期内未观察到机械性异常性疼痛,仅在第17天出现了一次机械性痛觉过敏；而初始体重为400 g的大鼠则在第17天表现出了机械性异常性疼痛,第8-26天表现出了机械性痛觉过敏,免疫荧光显示PTX处理组大鼠后足表皮下IENF断裂,IENF密度显著降低,电镜观察可见空泡变性的异常线粒体的比例升高,PTX处理组大鼠表现出明显的外周神经病变.结论 初始体重400 g的SD大鼠对PTX所致的外周神经病变较敏感,适合作为PTX所致外周神经病变的模型动物.

Establishment of Rat Model of Chemotherapy-induced Peripheral Neuropathy

Objective Chemotherapy-induced peripheral neuropathy （CIPN） is the common adverse reactions of mutiple chemotherapy drugs. At present, CIPN model is most commonly established by injecting paclitaxel （PTX） intraperitoneally to SD rats. However, those methods differ a lot and the influence factors are still unknown. Thus in this paper we aim to find the influence factors and optimize an ideal model for CIPN research. Methods SD rats were injected i.p. every other day with PTX. Mechanical allodynia and mechanical hyperalgesia effects were examined by the behavioral test. Intraepidermal nerve fiber （IENF） of the skin of hind foot was stained by immunofluorescence and morphology and number of mitoehondrial on the sciatic nerve was detected with electron microscopy. Results Injection of 2 mg.kg-I PTX for 4 times had no effect on the weight of SD rats. No obvious mechanical abnormalities pain and mechanical allodynia was observed during the 34 d experimental duration in rats with the initial weight of 200 g. While in rats with the initial weight of 400 g, mechanical abnormalities pain was observed at the 17d, and mechanical hyperalgesia lasted from the 8 d to the 26 d. At the same time, density of IENF under the skin was significantly reduced after PTX treatment, and the proportion of abnormal mitochondria was also increased, showing severe peripheral neuropathy. Conclusions Rats with initial body weight of 400 g are more sensitive to establish PTX-induced peripheral neuropathy and are more suitable for CIPN research.