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目的观察恒河猴黑质内注射脂多糖后运动行为和黑质多巴胺能神经元的变化,探讨脑内炎症反应在黑质多巴胺能神经元慢性变性过程中的作用。方法成年恒河猴5只,分别定位注射生理盐水(对照,编号M5)和脂多糖(存活24周:编号M1和M2,存活48周:编号M3和M4)。上述注射均在存活前0周、8周、16周,向右侧黑质部位注射3次,每次40μl(2.5g/L)。术后观察猴行为改变(包括随意运动和上肢活动),免疫组织化学染色观察黑质部位酪氨酸羟化酶阳性神经元的变化及小胶质细胞的激活情况。结果1.猴全身运动:注射脂多糖24周和48周后,各个动物运动距离和平均速度与术前自身相比随观察时间呈减少趋势,对照组动物两个指标与术前比较无变化。2.猴上肢活动:猴M1和M2,注射对侧前臂取食时间术后24周较术前分别延长了36.1%、27.1%,手爪抓取食物时间分别延长了41.2%、28.6%。猴M3和M4,注射对侧前臂取食时间术后48周较术前分别延长了76.5%(P<0.01)、50%(P<0.01),手爪抓取食物时间分别延长了81.8%(P<0.01)、55.6%(P<0.01),4只实验动物同侧上肢未见影响。3.注射脂多糖各个动物注射侧黑质阳性神经元数量与对侧相比较,有不同程度的减少,存活48周动物神经元减少更加明显;对照动物两侧黑质部位神经元数量无变化。4.注射脂多糖各个动物注射侧黑质部位小胶质细胞出现不同程度的激活,在24周组较明显。结论脂多糖诱导的炎症反应能引起猴黑质部位多巴胺能神经元的变性损伤和行为学的改变,这些改变呈慢性进展的特点,行为改变与多巴胺能神经元损伤程度相关。
Objective To observe the changes of motor behavior and dopaminergic neurons in rhesus monkeys injected with lipopolysaccharide (LPS) into the substantia nigra of substantia nigra and explore the role of inflammatory reaction in the process of chronic degeneration of dopaminergic neurons in substantia nigra. Methods Five adult rhesus monkeys were injected with normal saline (control, code M5) and lipopolysaccharide (24 weeks of survival: M1 and M2, respectively, for 48 weeks: M3 and M4). The above injections were all injected into the right substantia nigra site 3 times (2.5 g / L) three times before, during, and after 8 weeks and 16 weeks of survival. Postoperative monkeys were observed behavioral changes (including free exercise and upper limb activity), immunohistochemical staining tyrosine hydroxylase-positive neurons in the substantia nigra and the activation of microglia. Whole body movement of monkeys: After 24 and 48 weeks of injection of lipopolysaccharide, the movement distance and average velocity of each animal decreased with the observation time compared with the preoperative period. There was no change in the two indexes in the control group compared with that before operation. The activities of monkey’s upper limbs: monkey M1 and M2, the feeding time of contralateral forearm was 36.1% and 27.1% longer than preoperatively at 24 weeks after operation, respectively, and the time for grasping food by hand was prolonged by 41.2% and 28.6% respectively. In the monkeys M3 and M4, the time of feeding on the contralateral forearm was prolonged by 76.5% (P <0.01) and 50% (P <0.01), respectively, and the time taken by the claws was prolonged by 81.8% P <0.01), 55.6% (P <0.01). No significant difference was observed in ipsilateral upper limbs of 4 experimental animals. The numbers of substantia nigra positive neurons in the injected side of each animal injected with lipopolysaccharide decreased to some extent compared with the contralateral ones, and the decrease of the neurons in the 48-week survival animals was more obvious. The number of neurons in the substantia nigra was not changed on both sides of the control animals. Injection of lipopolysaccharide in each side of the animals injected with substantia nigra microglia showed varying degrees of activation in the 24-week group was more obvious. Conclusion The inflammatory reaction induced by lipopolysaccharide can cause degeneration damage and behavioral changes of dopaminergic neurons in the substantia nigra of monkey. These changes are characterized by chronic progressive changes. The behavioral changes are related to the degree of dopaminergic neuron injury.