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目的:观察偏侧帕金森病样大鼠微囊化牛嗜铬细胞脑移植后多巴胺及其代谢产物含量的变化,探讨大鼠异常旋转行为改善的可能途径。方法:实验于1999-01／12在解放军总医院老年医学研究所完成。选择 6-羟基多巴立体定向损毁右侧黑质诱发的偏侧帕金森病样雌性SD大鼠30只,随机分为2组,微囊组20只,对照组10只。微囊组大鼠水合氯醛麻醉后于右侧纹状体立体定向植入约200个以海藻酸钠-多聚赖氨酸-海藻酸钠为材料含牛嗜铬细胞的微胶囊,对照组大鼠未做脑内移植手术。观察移植术前后阿朴吗啡(0．5 mg／kg)诱发的大鼠旋转行为。利用微透析技术采取帕金森病样大鼠脑纹状体区细胞外微透析液,用高效液相电化学层析法测定对照组大鼠在6-羟基多巴损毁右侧脑黑质后 16周时及两组大鼠在牛嗜铬细胞移植后12周时脑纹状体区细胞外液中单胺类物质含量的变化。结果:纳入偏侧帕金森病样大鼠30只,实验过程中微囊组麻醉意外、脑出血、肢体癫痫样抽搐死亡4只,对照组脑出血、不明原因死亡2 只。进入结果分析微囊组和对照维分别为16和8只大鼠。①微囊组移植后1周开始阿朴吗啡诱发的异常旋转次数明显减少,作用持续6个月以上(F=37．89,P<0．01)。②对照组帕金森病样大鼠右侧脑黑质损毁后16周时右侧脑纹状体区细胞外液中3,4-二羟基苯乙酸和高香草酸水平较左侧明显降低(t=7．012,4．394,P<0．01),右侧脑上述物质含量仅为左侧脑的8％和12％。③移植后12周,微囊组帕金森病样大鼠右侧脑纹状体区细胞外液中3,4-二羟基苯乙酸、高香草酸和5-羟基吲哚乙酸水平较对照组显著升高(t=4．273,4.402,6．445,P<0．01),分别提高了 3．1,5.3和2．7倍。结论:帕金森病样大鼠黑质损毁侧纹状体区多巴胺类物质含量明显降低, 移植微囊化牛嗜铬细胞后含量升高,使帕金森病样大鼠的运动功能障碍明显改善。
OBJECTIVE: To observe the changes of dopamine and its metabolites after cerebral transplantation of microencapsulated bovine chromaffin cells in parkinsonian rats, and to explore the possible ways of improving the abnormal rotation behavior in rats. METHODS: The experiment was performed at the Institute of Geriatrics, PLA General Hospital from January 1999 to December 1999. 30 SD rats with hemiparkinsonism induced by right substantia nigra of 6-hydroxydopamine were randomly divided into 2 groups, 20 in the microcapsule group and 10 in the control group. The rats in the microcapsules group were implanted with about 200 microcapsules containing bovine chromaffin cells with sodium alginate-polylysine-sodium alginate as the material, and the control group Rats have not undergone intracerebral transplantation. The morphological changes of rats induced by apomorphine (0.5 mg / kg) before and after transplantation were observed. The microdialysis technique was used to take extracellular microdialysates in the striatum of striatum in Parkinson’s disease-like rats. The contents of extracellular microdialysates in the striatum of Parkinson’s disease-like rats were determined by high performance liquid chromatography (HPLC) Changes of monoamine concentration in extracellular fluid of brain striatum at week 12 and 12 weeks after bovine chromaffin cell transplantation in rats. Results: 30 hemiparkinsonian rats were included in the study. During the experiment, 4 rats died of cerebral hemorrhage and epileptic seizures in the microcapsule group, 2 in the control group with intracerebral hemorrhage and 2 unexplained deaths. Into the results of analysis of the microcapsule group and the control dimension were 16 and 8 rats. ① The number of abnormal rotation induced by apomorphine in the microcapsule group decreased significantly after 1 week, and the effect continued for 6 months (F = 37.89, P <0.01). ② In the control group, the levels of 3,4-dihydroxyphenylacetate and homovanillic acid in the extracellular fluid in the right striatum were significantly lower than those in the left side at 16 weeks after the right substantia nigra was damaged in the Parkinson’s disease-like rats (t = 7.012,4.394, P <0.01), the right brain content of the above substances only 8% and 12% of the left brain. ③ After 12 weeks of transplantation, the levels of 3,4-dihydroxyphenylacetate, homovanillic acid and 5-hydroxyindoleacetic acid in the extracellular fluid of right striatum of Parkinson’s disease-like rats in the microcapsule group were significantly higher than those in the control group (T = 4.273, 4.402, 6.445, P <0.01), increased by 3.1, 5.3 and 2.7 times respectively. CONCLUSION: The dopamine levels in the lesioned striatum of the substantia nigra in Parkinson’s disease-like rats were significantly decreased. The content of dopamine increased after transplantation of microencapsulated bovine chromaffin cells, which markedly improved the motor dysfunction in Parkinson’s disease-like rats.