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目的探讨纹状体内双靶点注射6-羟基多巴(6-hydroxydopamine,6-OHDA)制备帕金森病大鼠模型的可行性。方法将52只体质量(220±10)g的雄性Wistar大鼠随机分为模型制作组(32只)、假手术组(10只)和正常对照组(10只)。应用脑立体定位技术将6-OHDA分两点注入大鼠右侧纹状体(每点10μl),假手术组注射等量生理盐水。术后以阿朴吗啡检测其异常旋转行为,2个月后观察病理切片行纹状体和黑质的HE及TH免疫组化染色,以及多巴胺能神经元的改变并计数。结果32只模型制作鼠中,共有22只在阿朴吗啡多次注射后,获成功模型。光镜下,HE及TH免疫组化染色可见模型组左侧黑质致密带(SNc)的多巴胺能神经元数量较多,呈带状斜行排列。右侧多巴胺能神经元几乎消失,残存神经元萎缩。左右两侧差异有统计学意义(P<0.01)。结论纹状体内双靶点注射6-OHDA可以造成与PD患者基本相似的病理特征,且模型制作稳定好、成功率高。
Objective To investigate the feasibility of injecting 6-hydroxydopamine (6-OHDA) into the striatum to produce a rat model of Parkinson’s disease. Methods Fifty-two male Wistar rats weighing 220 ± 10 g were randomly divided into model group (32 rats), sham operation group (n = 10) and normal control group (n = 10). The brain stereotactic technique was used to inject 6-OHDA into the right striatum (10μl per mouse point) in two points. The sham operation group was injected with the same amount of saline. Postoperatively, apomorphine was used to detect abnormal rotation behavior. HE and TH immunohistochemical staining of striatum and substantia nigra after 2 months were observed, and changes of dopaminergic neurons were counted. Results Twenty-two of the 32 model mice were successfully injected with apomorphine after repeated injections. Light microscope, HE and TH immunohistochemical staining showed that the left substantia nigra compact zone (SNc) in the model group, the number of dopaminergic neurons in a more oblique distribution. Right dopaminergic neurons almost disappeared, residual neuronal atrophy. The left and right differences were statistically significant (P <0.01). Conclusions The double target injection of 6-OHDA in the striatum can cause pathological features similar to those of PD patients. The model is stable and the success rate is high.