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本文通过锰诱导多巴胺能神经元凋亡及其可能的神经化学机制的研究 ,进而探讨锰中毒与帕金森病发病的相互关系。分离培养大鼠中脑黑质多巴胺能神经元用不同剂量 Mn Cl2 处理后 ,用荧光染料进行染色 ,观察了凋亡神经元数量。用腹腔注射及脑内单侧注射 Mn Cl2 染毒方法处理大鼠 ,并采用脑内微透析技术和高效液相色谱 -电化学方法 (HPLC-ECD)在活体检测了术后不同时间的纹状体细胞外液中 DA及其代谢产物 DOPAC、HVA以及 5 -HT的代谢产物 5 -HIAA等的含量 ;同时作丙二醛含量和过氧化物歧化酶活性检测。结果发现 ,凋亡神经元的细胞核缩小、不规则、染色质呈块状深染 ,凋亡细胞数量随 Mn Cl2 剂量升高而增多。Mn Cl2 脑内注射侧与注射对侧相比 ,术后 4、7、10、2 0 d的 DA、DOPAC、HVA和 5 -HIAA含量均有不同程度的降低。腹腔染毒高、低剂量组 2 0 d后大鼠整体纹状体匀浆的上述指标也明显降低。此外 ,染毒大鼠纹状体中丙二醛水平随染毒剂量增高而增高 ,过氧化物歧化酶活性随染毒剂量增高却下降。以上结果表明 ,锰中毒可能是引起帕金森病发病的原因之一
In this paper, manganese induced dopaminergic neuronal apoptosis and its possible neurochemical mechanism, and then explore the relationship between manganese poisoning and the incidence of Parkinson’s disease. After isolated and cultured rat substantia nigra dopaminergic neurons were treated with different doses of MnCl 2, they were stained with fluorescent dye and the number of apoptotic neurons was observed. The rats were treated with intraperitoneal injection of Mn Cl2 and intracerebroventricular injection of MnCl2, and the morphology of the striatum was detected in vivo by HPLC-ECD and intracerebral microdialysis technique. The content of DA and its metabolites DOPAC, HVA and 5-HIAA metabolites in somatic cell extracellular fluid were measured. Meanwhile, the content of malondialdehyde and the activity of superoxide dismutase were detected. The results showed that the nuclei of apoptotic neurons were reduced and irregular, chromatin was deeply stained, and the number of apoptotic cells increased with the increase of MnCl2 dose. The levels of DA, DOPAC, HVA and 5-HIAA at 4, 7, 10 and 20 d after operation in Mn Cl2 injection group were decreased to some extent compared with the contralateral injection. Intraperitoneal injection of high and low dose groups 20 days after the whole rat striatum of the above indicators were significantly reduced. In addition, the level of malondialdehyde in striatum increased with the increase of exposure dose and the activity of superoxide dismutase decreased with the increase of exposure dose. The above results show that manganese poisoning may be one of the causes of Parkinson’s disease