重组人改构体酸性成纤维细胞生长因子减少帕金森病大鼠黑质酪氨酸羟化酶免疫阳性神经元丢失

MODIFIED RECOMBINANT HUMAN aFGF PROTECTS TYROSINE HYDROXYLASE NEURONS IN SUBSTANTIA NIGRA OF PARKINSON DISEASE RATS FROM LOSS

目的探讨重组人改构体酸性成纤维细胞生长因子(Mrh-aFGF)对帕金森病(PD)大鼠旋转行为和酪氨酸羟化酶(TH)免疫阳性神经元的影响。方法6-OHDA分别注入黑质和腹侧被盖区后建立PD大鼠模型,侧脑室内注射Mrh-aFGF,用阿扑吗啡诱导旋转行为,免疫细胞化学染色观察TH免疫阳性神经元和纤维,并进行定量分析。结果对照组均未引出旋转行为;PD组术后旋转启动时间缩短,持续时间延长,速度加快;生理盐水(NS)处理组旋转行为未见明显改善;Mrh-aFGF处理组旋转启动时间延长,持续时间缩短,速度减慢(P<0.01)。各组大鼠健侧黑质TH阳性神经元的数量维持在相近的水平。同组内健侧和损毁侧阳性神经元比较,对照组损毁侧无明显改变;PD组、NS处理组和Mrh-aFGF处理组损毁侧阳性神经元与健侧比较均明显减少(P<0.01)。其中PD组损毁侧黑质TH免疫阳性神经元数量随时间延长逐渐减少(P<0.01)。NS处理组损毁侧黑质TH免疫阳性神经元的变化与PD组相似;Mrh-aFGF处理组损毁侧黑质阳性神经元较PD组及NS处理组有明显改善,阳性神经元的数量明显增加(P<0.01)。结论Mrh-aFGF能减少PD大鼠黑质TH免疫阳性神经元的丢失,并改善其旋转行为。

Objective To observe the changes of rotation behavior and tyrosine hydroxylase immunopositive neurons and investigate how Mrh-aFGF affects them in substantia nigra of Parkinson disease rats. Methods After building a rat model of Parkinson disease by injecting 6-OHDA into substantia nigra and ventral tegmental area, we used Mrh-aFGF to intervene rats by lateral ventricle injection to observe how behavior of rats induced by apomorphine and tyrosine hydroxylase immunopositive neurons in substantia nigra of rats changes, then quantitatively analyzed the change of tyrosine hydroxylase immunopositive neurons. Results Rotation behavior was not found in control group, otherwise, actuation time was shorted, time length was prolonged, and average velocity of rotation was accelerated in Parkinson disease rats（ P 〈 0.01 ）. Compared with PD group, rotation behavior of rats treated by using NS was not improved, however, rats treated with Mrh-aFGF, showed lengthened actuation time, shorted time length and velocity（ P 〈 0.01 ）. With regard to immunopositive neurons of tyrosine hydroxylase, their numbers kept in a similar level in uninjured side of all groups, and no changes were found in bilateral substantia nigra of control group, however, the immunopositve neurons were decreased significantly in Parkinson disease, NS and Mrh-aFGF group （ P 〈 0.01 ）. Regarding the injured side, tyrosine hydroxylase immunopositive neurons were gradually decreased in PD group（ P 〈 0.01 ）, and similar changes were manifested in NS group. After treated with Mrh-aFGF, the structure of substantia nigra was significantly improved and the number of tyrosine hydroxylase neurons was increased, compared with Parkinson disease and NS group（ P 〈 0.01 ）. Conclusion Mrh-aFGF could protect immunopositive neurons of tyrosine hydroxylase from loss and improve the rotation behavior of Parkinson disease rats.