| Objective: Our experiment was to discuss the neuroprotective effects and possible mechanism of nonmitogenic aFGF in Parkinson's disease by observing the changes of behavior, histopathoiogy and tyrosine hydroxylase (TH) immunoreactive (TH-IR) neurons in the substantia nigra (SN) and ventral tegmental area (VTA) of Parkinson's disease rat model.Methods: 72 SD rats were divided randomly into 4 groups: (1) the control group: injected 6 ul natural saline (NS) into the left substantia nigra pars compacta (SNC) and VTA. (2) PD group: injected 6-OHDA into the left SNC and VTA to produce PD rat model. (3) PD+NS group: produce PD rat model, then injected 10 ul NS into the right lateral ventricle at 2 days interval. (4) PD+aFGF group: produce PD rat model, then injected 10 μl(0.2 μg/μl) nonmitogenic aFGF into the right lateral ventricle at 2 days interval. To observe the behavioral changes of the rats, then at the end of 1, 2, 4 week, the equal number of rats in every group were sacrificed (n=6 each time). The changes of histopathoiogy, TH-IR neurons in the SN and VTA and ultrastructure of the substantia nigra (SN) were observed.Results: (1) The behavioral changes: In PD group and PD+NS group, the start time of PD rats shortened gradually, the continuous time lengthened, and the rotation rate speeded by degrees. The rotary behavior became invariable until 2 weeks after injection. In PD+aFGF group, the rotary behaviors bettered and have the significant difference compared to PD group and PD+NS group, 2 weeks later. (2) The histopathological changes: the number of neurons in the left SN and VTA of PD rats in PD, PD+NS and PD+aFGF group, decreased significantly compared to right side throughout the test time. Compare the number of neurons in the left SN and VTA between all groups, 2 or 4 weeks after injection decreased significantly compared to 1 week after injection in PD group and PD+NS group; Compare PD+aFGF group with PD group or PD+NS group, the number of neurons increased and have the significant difference. The nigral neurons of rats in PD group appeared karyopyknosis, mitochondria swollen, crista lost, endoplasmic reticulum was found to be dilatated,obvious degranulation, the membranes of pre-synaptic and post-synaptic were not clear and the synaptic space disappeared. In PD+aFGF group, the ultrastructure of nigral neurons such as nuclei, mitochondria, synaptic structure, bettered significantly compared to PD group. (3) Changes of the TH-IR neurons: the number of TH-IR neurons in the left SN and VTA of PD rats in PD, PD+NS and PD+aFGF group, decreased significantly compare to right side throughout the test time. Compare the number of TH-IR neurons in the left SN and VTA between all groups, 2 or 4 weeks after injection decreased significantly compared to 1 week after injection in PD group and PD+NS group; Compare PD+aFGF group with PD group or PD+NS group, the number of TH-IR neurons increased and have the significant difference. Conclusions: (1) Unilateral injection of 6-OHDA into the SNC and VTA may improve the success rate in making PD rat model. Add the amount of 6-OHDA may shorten the time. (2) PD rats have serious behavioral changes, the number of TH-IR neurons in the left SN and VTA decreased significantly, which showed that the DA production decreased, maybe the imbalance of nigrostriatal neurotransmitte is an important factor in PD. (3) Nissl staining neurons in the left SN and VTA were lost markedly. The ultrastructural changes of the nigral neurons exhibited karyopyknosis, swollen mitochondria, lost crista. Endoplasmic reticulum was found to be dilatated, obvious degranulation. These results showed that the ultrastructural changes maybe contributes to the death and loss of neurons. (4) The nonmitogenic aFGF may better the rotary behavior, decrease nigral neurons loss, and improve the ultrastructure of nigral neurons markedly. (5) The nonmitogenic aFGF may increase the number of the survival TH-IR neurons, protect the dopaminergic neurons, and enhance the DA production. |
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