开野实验与阿朴吗啡诱导旋转实验在评价大鼠黑质毁损程度中的作用比较

Two praxiological methods in evaluation the substantia nigra compacta lesion size of rats

目的观察黑质多巴胺能(DA)神经元毁损大鼠行为学和形态学变化特点,探讨两者之间的相关性,寻找一种能敏感反应DA毁损程度的行为学指标。方法利用6-羟基多巴胺(6-OHDA)单侧一点注射大鼠黑质致密区(SNc),特异毁损DA能神经元,采用开野实验和阿朴吗啡(APO)诱导的旋转实验观察术后不同时间点行为学变化;利用N issl染色、HE染色、免疫组织化学方法,观察各时间点黑质形态学变化。结果术后1 d约50%黑质DA神经元丢失,21 d毁损比近90%;开野实验中旋转、探究、后肢站立和穿梭行为在术后1 d即有显著改变,与毁损程度有良好的相关性(r分别为0.471、-0.719、-0.589、-0.594,P<0.01),在3 d、5 d时有恢复倾向,修饰行为与毁损程度无相关性(r=-0.227,P>0.05)。术后7 d大鼠出现APO诱导旋转行为,14 d转速>7圈/m in,与毁损程度呈正相关(r=0.942,P<0.01),没有改善迹象。结论开野实验可作为评价黑质毁损程度的敏感行为学指标。

Objective To observe the characteristics of praxiology and morphology of 6-hydroxydopamine （6-OHDA） lesioned rats and the relation between them; and to seek a sensitive behavioral parameter in evaluation DA degenerative degree. Methods Rats received a unilateral injection of 6-OHDA into the substantia nigra pars compacta （SNc）. Behavioral changes and dopaminergic degeneration were observed with the open-field test, apomorphine （APO） induced turning, HE and Nissl body staining, and immunocytochemistry methods 1 d, 3d, 5d, 7d, 14d, 21d after lesion. Results Nearly 50% dopaminergic neurons lossed in ipsilateral SNc on ld while approximately 90% on 21d. All parameters of open-field test except grooming had a notable alternation ld after lesion （ P 〈 0.05 ） . The correlational analyses yielded a positive relationship between turning and lesion size （ r = 0. 471, P〈0.01 ）, while scanning,rearing and locomotor activity were negatively correlated with lesion size （ r= - 0.719, r= -0.589, r= -0.594, P〈0.01 ） . There was an obvious tendency of recovery on 3d and 5d. APO induced turning commenced 7d after lesion, which the velocity exceeded 7circles/min on 14d, and positively correlated with DA level（ r = 0.942, P 〈 0.01 ）, but no recovery exhibited. Conclusion The open-field test is a sensitive behavioral parameter to predict degree of DA deletion.