6-羟基多巴胺诱发帕金森病大鼠模型的制作和评价

目的 向大鼠中脑黑质区注入6-羟基多巴胺(6-OHDA)建立帕金森病(PD)大鼠模型,并从行为学(ethology)及组织病理、生化角度对该模型进行评价.方法 将6-OHDA立体定向微量注入大鼠右侧中脑黑质(SN)区,观察阿朴吗啡(APO)诱发的大鼠旋转行为及黑质细胞形态学变化,测定脑组织液中儿茶酚胺类物质含量及黑质酪氨酸羟化酶的免疫活性.结果 120只大鼠中经APO诱导后有67只(占55.8%)持续转向健侧(旋转圈数＞7r/min),帕金森病大鼠模型复制成功.PD鼠注射侧黑质区多巴胺能神经元数量较对侧明显减少,体积缩小,结构欠清晰.注射侧脑组织液中多巴胺(DA)、3,4-二羟基苯酸(DOPAC)、高香草酸(HVA)、5-羟色胺(5-HT)含量均低于对侧,注射侧黑质致密部酪氨酸羟化酶(TH)免疫阳性细胞较健侧明显减少.连续观察10个月,PD模型大鼠的异常旋转行为无自发性恢复.结论 用6-OHDA选择性损毁大鼠黑质多巴胺能神经元,可造成与PD患者相似的基本病理变化,建立起可靠而稳定的PD大鼠模型.

Reproduction and evaluation of 6-OHDA-induced rat model of Parkinson's disease

Objective To replicate Parkinson's disease (PD) rat model by injecting 6-hydroxydopamine (6-OHDA) into substantia nigra (SN) of rat's midbrain, and to evaluate the model with the criteria of ethology, histopathology and biochemistry. Methods A PD rat model was replicated by stereotaxic microinjection of 6-OHDA into substantia nigra (SN) of rat's right midbrain. Changes in both the rat's behavior pattern after injecting apomorphine (APO) and the cerebral black substance cells were observed. The content of monoamine substances in the extracellular fluid (ECF) was measured, and the changes in the immunological activity of tyrosine hydroxylase (TH) in substantia nigra were also determined. Results There were 67 (55.8%) rats among 120 rats which were injected apomorphine (APO) showed steady rotation to the left (the rotation time >280r/40min). So the PD model was regarded eligible. In the site of lesion in SN, the number and volume of dobaminergic neurons were decreased, and the tissue structure of SN became indistinct, the levels of dopamine (DA), dihydroxyphenylaceticacid (DOPAC), homovanillicacid (HVA) 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleaceticacid (5-HIAA) were more conspicuously reduced than that in uninjured side. TH-immunoreactive cells of substantia nigra compact part were lessened obviously on injured side. The abnormal rotatory behavior of PD rats did not spontaneously disappear during 10 months of continuous observation. Conclusion The PD rat model, which is reproduced by injecting 6-OHDA to selectively destroy dopaminergic neurons in the substantia nigra of rat, is stable and reliable, and demonstrated similar primary pathological changes of PD.