脂多糖注入黑质对恒河猴运动行为和多巴胺能神经元的影响  

THE INFLUENCE OF INTRA-NIGRAL INJECTION OF LIPOPOLYSACCHARIDE ON THE MOTOR BEHAVIOR AND DOPAMINERGIC NEURONS IN THE MONKEY

作　　者：陈庆友[1] 刘玉军[1] 鲁强[1] 户乃丽[1] 徐群渊[1] 张进禄[1] 

机构地区：[1]首都医科大学北京神经科学研究所北京市神经再生修复研究重点实验室教育部神经变性病学重点实验室,北京100069

出　　处：《解剖学报》2008年第4期481-487,共7页Acta Anatomica Sinica

基　　金：北京市自然科学基金资助项目(7062008);北京市优秀人才项目(20042D050182)资助

摘　　要：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 effects of intranigral injection of lipopolysaccharide （LPS） on the motor behavior and dopaminergic neurons （DA） in the brain of rhesus monkey, in order to explore the mechanism of inflammation in the progressive degeneration of the dopaminergic neurons. Methods Five adult rhesus monkeys（Macaca, M1-M5, 4 males and lfemale）were taken for the experiments. Among them 4 monkeys were intranigrally injected with LPS and survived 24 weeks （Mland M2） and 48 weeks （M3 and M4） respectively after the operation. One monkey （M5） was only injected with saline as a control animal. The injections （LPS or saline） were stereotaxically made 3 times Cat weeks 0, 8, 16 respectively; 40μl for each） in the substantia nigra on one side. Moving distance and speed were measured by Ethovison software . The movement time of upper limbs was recorded by using a Monkey Automated Movement Assessment Panel. The number of tyrosine hydroxylase （TH）- positive neurons and microglia in the substantia nigra was demonstrated by immunohistochemistry staining. Results 1 .The tests of locomotion distance and speed in the monkeys decreased apparently after the injection of LPS （24 and 48 weeks） as compared with that in the control animal. 2. The movement time of the upper limb opposed to the injection side decreased also apparently： For M 1 and M2, the arm movements were prolonged by 36.1% and 27.1%; the hand movements were prolonged by 41.2% and 28.6% ; for M3 and M4, the arm movements were prolonged by 76.5% （ P 〈 0.01） and 50% （ P 〈 0.01）, and the hand movements were prolonged by 81.8 % （ P 〈 0.01 ） and 55.6 % （ P 〈 0.01 ）. No changes could be seen in the limbs, ipsilateral to the injection, neither in the control case, M5. 3.The number of TH-positive neurons in the injected substantia nigra decreased to some degrees, which was more obvious in the cases of M3 and M4. 4.The microglia were activated in the area in all LPS-injected cases especially in the cases of M1

关 键 词：脂多糖 黑质 行为 酪氨酸羟化酶 免疫组织化学 恒河猴 

分 类 号：R742.5[医药卫生—神经病学与精神病学]