不同剂量6-羟基多巴胺注射大鼠单侧前脑内侧束后对中脑多巴胺能神经元损伤作用的观察

Injections of Various Doses of 6-hydroxydopamine in Medial ForebrainBundle Cause Different Extent of Lesions among the Subpopulations ofDopaminergic Neurons in Rat Ventral Midbrain

将不同剂量的６－羟基多巴胺（６－ＯＨＤＡ）注入大鼠一侧黑质（ＳＮ）头端的前脑内侧束（ＭＦＢ），４７天后用酪氨酸羟化酶（ＴＨ）免疫细胞化学染色法，观察旋转鼠整个ＳＮ和腹侧被盖区（ＶＴＡ）不同切面上ＤＡ神经元的损伤程度，结果发现：损伤侧ＳＮ和ＶＴＡ的ＴＨ阳性神经元数在所有观察水平上均有明显下降，并从前囟后５．１ｍｍ开始呈现６－ＯＨＤＡ剂量依赖性。而下降率（与健侧相比）为ＳＮ致密部（ｓｎｃ）＞网状部和外侧部（ｓｎｒ＋ｓｎｌ）＞ＶＴＡ。同时还发现，ｓｎｃ的ＴＨ阳性细胞在黑质两端分布比率较高，而ＶＴＡ的相应细胞在黑质中部分布率较高。另外，在健侧前囟后４．８ｍｍ处出现非６－ＯＨＤＡ剂量依赖性的ＴＨ阳性神经元计数明显增加的现象。本文的结果提示：６－ＯＨＤＡ对中脑ＤＡ神经元的总体损伤程度取决于多种因素，如６－ＯＨＤＡ剂量、神经元对６－ＯＨＤＡ的敏感度以及敏感神经元的分布等。同时健侧中脑组织对邻侧发生的损伤并非毫无反应。

Various doses of 6-hydroxydopamine were singularly injected into oneside of rat medial forebrain bundle. Fourty seven days later, the tyrosine hydroxylase (TH) positive cells of the midbrain oftheapomorphineinducedrotationalratswerecountedatsixlevelsofsectionsfrom -4.5mm to -6.0mm (to bregma). The results are: (1) a significant decline of total number of THpositive neurons was found on lesioned side in all 6-OHDA doses treated and a dose-dependent effect appeared after 5.1mm posterior to bregma, (2) the rate of the decline of THpositive neurons in lesioned side vs. unlesioned side assumed an order of substantia nigra pars compacta (SNC)>pars reticulata+pars lateralis (SNR+SNL)>ventral tegmental area (VTA), and an order of rostral>caudal>middle part of substantia nigra, and (3) the SNC of unlesioned side responsed to the contralateral injection of 6OHDA by an non-dose-dependent increase of THpositive neuron counts at -4.8mm (to bregma) sections, which was significant more than the vehicletreated control. This study suggests that the extent of lesion of rat ventral midbrain by 6-OHDA injection may be determined by several aspects, such as the dose of 6-OHDA、the vulnerability of the neurons to 6-OHDA、the distribution of the neurons that susceptibe to 6-OHDA and even the activity of the unlesioned dopaminergic neurons.