6-羟基多巴胺损伤早期帕金森病大鼠模型的实验研究

摘要

目的：观察6-羟基多巴胺（6-hydroxydopamine，6-OHDA）损伤早期帕金森病（Parkinson's disease， PD）大鼠行为学及黑质部位组织学的变化特点。方法偏侧前脑内侧束注射6-OHDA，通过阿扑吗啡诱发旋转试验、跨步调节试验和姿势部对称试验评估注射后24 h、7 d及28 d大鼠行为学的变化；通过免疫组织化学染色观察黑质部位酪氨酸羟化酶(tyrosine hydroxylase， TH)阳性细胞计数的变化。结果6-OHDA组大鼠跨步调节试验评分减少，姿势不对称试验评分增加，阿扑吗啡诱发大鼠向损伤对侧旋转，与对照组和假手术组比较统计学差异显著（P<0.05）；6-OHDA 7 d组、28 d组与24 h组比较，跨步调节试验评分进一步减少、姿势不对称试验评分进一步增加，阿扑吗啡诱发旋转次数增加，有统计学差异（P<0.05）；6-OHDA 24 h组黑质TH阳性细胞减少，与对照组和假手术组比较有统计学差异（P<0.05），7 d组及28 d组TH阳性细胞进一步减少，与24 h组比较统计学差异显著（P<0.05）。结论通过阿扑吗啡诱发旋转结合非药物诱发试验进行行为学评估，可确定偏侧前脑内侧束注射6-OHDA损伤早期帕金森病动物模型。%ObjectiveTo observe the characteristic changes of behaviors and substantia nigra (SN) histology of Parkinson's disease (PD) rat model induced by 6-OHDA. Methods 6-hydroxydopamine (6-OHDA) was injected into the rats' unilateral medial forebrain bundle. The behaviors of the rats on the 24th hour ,7th day and 28th day were assessed by tests of the apomorphine induced rotations, the adjusting steps and the postural asymmetry.The forms and counts of tyrosine hydroxylase positive (TH) cells were surveyed by the immunohistochemistry staining. Results Rats of PD models appeared significant decrease in score of the adjusting steps test, while increase in score of the postural asymmetry test, and rotated to the uninjured side induced by apomorphine, compared with rats of control and sham groups (P<0.05). It was significantly aggravated the behavior of PD models of 7d and 28d groups compared with 24h group (P<0.05). The counts of TH-positive cells in SN of rats of 24h group significantly decreased compared with rats of control and sham groups (P<0.05), and the counts of 7d and 28d groups decreased further compared with 24h group (P<0.05). Conclusions Early injured PD rat model, induced by injecting 6-OHDA into the unilateral medial forebrain bundle, can be demonstrated by passing through apomorphine induced rotational test associate nonmedicine induced behavioral tests.