鱼藤酮对SD大鼠脑组织神经元损伤的初步研究

Preliminary study on damage of neurons in brains of SD rats by rotenone

目的通过对鱼藤酮导致慢性中毒SD大鼠脑组织标本的病理学检测,探讨鱼藤酮损伤脑神经元的作用机制。方法将20只雄性SD大鼠随机分为两组,实验组:1.5 mg/(kg·d)的鱼藤酮颈背部皮下注射8周,共10只;对照组:相同体积的葵花油颈背部皮下注射8周,共10只。实验中观察各组大鼠的一般情况并每周进行行为学测试及体重的测量。选取实验组全部存活的SD大鼠脑组织标本,共6个;在对照组中随机选取6个脑组织标本。随后进行HE染色,并用显微镜观察组织的病理变化。结果实验结束时,实验组大鼠共死亡4只,对照组无死亡现象。实验组大鼠在实验中表现出较为明显的毛色泛黄、反应迟钝、精神萎靡、活动减少、进食缓慢等中毒症状。在体重增长速度上与对照组比较,差异有统计学意义(P<0.05)。在行为学上,实验组大鼠在网格实验中表现出了较为明显的行为学异常,第7、8周时两组大鼠移动的潜伏时间比较,差异有统计学意义(P<0.05)。大鼠脑病理学检测提示实验组大鼠脑干区可见神经元数目减少、核固缩、变性等改变。黑质致密部多巴胺(dopanine,DA)神经元变性。对照组大鼠未见明显异常。结论鱼藤酮导致慢性中毒的SD大鼠脑组织神经元发生损伤,并出现神经系统相关的行为学表现,推测鱼藤酮造成线粒体损伤是导致神经元变性坏死的主要原因。

Objective To study the damage of neurons in the brains of SD rats by rotenone, we investigate themechanism of rotenone on damage of neurons in brains. Methods A total of 20 male SD rats were randomly divided into anexperimental group and a control group with 10 rats in each group. The rats in the experimental group received a subcutaneousinjection of 1.5 mg/（kg.d）rotenone and the rats in the control group received a subcutaneous injection of the same volume ofsunflower oil, all for 8 weeks. During the period of the experiment, the general conditions of the rats in each group wereobserved and the simple behavioral tests were performed. The brain tissues of all the alive rats in the experimental group and 6rats randomly selected in the control group were collected and microscopically observed with HE staining for their pathologicalchanges. Results At the end of the experiment, 4 rats were dead in the experimental group, and no rats were dead in thecontrol group. In the experimental group, the rats showed obvious poisoning symptoms, such as the yellow hair, slow response,listlessness, decreased activity, eating slowly, etc. Compared with the rats of the control group, the body growth was slow in therats of the experimental group（P〈0.05）. The rats of the experimental group also showed obvious abnormal behavior in thegrid experiment, and the latent time of movement in two groups at 7th and 8th week,which had a significant differencecompared with the behavior of the rats of the control group（P〈0.05）. The pathology detection showed that the number of theneurons was decreased obviously, there were karyopyknosis and cell degeneration, etc. in the brain stem region, and dopamineneurons degeneration in the substantia nigra compacta in the experimental group rats. No obvious abnormal changes were foundin the control group rats. Conclusions The rotenone could damage the neurons in the brain of SD rats, and the rats showrelated abnormal behavior and symptoms. We speculate that the main cause of the damage of neurons in the brain may be themitochondrial damage induced by rotenone.