鱼藤酮致大鼠脑内α-突触核蛋白的表达分布变化

目的 研究鱼藤酮所致的帕金森病大鼠的脑内α-突触核蛋白（α—synuclein,ASN）分布。方法 Wistar大鼠随机分成两组,分别给予鱼藤酮和／或溶剂（对照组）皮下注射,4周后取脑组织,对黑质部位HE染色,光镜下观察Lewy小体形态;对黑质、海马、纹状体等脑区进行酪氨酸羟化酶（tyrosine hydroxylase,TH）、ASN免疫组织化学染色。结果 在对照组大鼠脑内,ASN广泛分布于各脑区,尤其在皮质、纹状体、海马等纤维投射丰富的区域。鱼藤酮处理的大鼠脑中,黑质TH阳性多巴胺能神经元数目减少、纹状体区TH阳性纤维脱失,黑质部位可见Lewy小体样结构;ASN阳性染色在各个脑区均有增强但各个脑区增强程度不一,黑质部位神经元胞浆和胞核内均有ASN明显聚集,纹状体可见ASN聚集围绕在细胞周围。海马部位偶见ASN在胞浆中点状聚集,胞核中无明显改变。结论 在鱼藤酮皮下注射导致的帕金森病大鼠的脑内,ASN在多个脑区中表达增加,而在黑质纹状体部位聚集最为明显,蛋白分布由多巴胺能神经元的突触末端向胞浆和胞核扩展。

alpha-Synuclein redistributed and aggregated in rotenone-induced Parkinson's disease rats

Objective To observe the influence of rotenone on the distribution of alpha-synuclein (ASN) in rat model of Parkinson's disease (PD). Methods Wistar rats were randomly divided into two groups and received 2 mg/kg rotenone (s.c.) or sunflower oil (as control group) for about 4 weeks. The hippocampus, substantia nigra and striatum of brain were observed. Hematoxylin and eosin stain were used to observe the Lewy body like inclusion. The expression of tyrosine hydroxylase (TH) or ASN protein was determined by anti-TH or anti-alpha-synuclein immunohistochemistry, respectively. Results In control rats, ASN protein distributed widely in brain, especially in hippocampus, cortex and striatum. Rotenone obviously increased TH positive neurons and fibers loss in substantia nigra and striatum (P < 0.05). In rotenone treated rats, ASN positive cells increased in global brain but not distributed in an even manner. In substantia nigra, ASN positive stuff was found aggregate in both cytoplasm and nucleus, and some formed spherical inclusion; in striatum, ASN positive neurites end aggregated and agglomerated around neurons; and in hippocampus, few dot-like ASN were aggregated in cell body, and no notable change was found in nucleus. Conclusion In rotenone administrated PD rats, ASN protein aggregated in several brain regions but most obviously in striatum and substantia nigra, and the distribution region of ASN was changed from peri-synapse to the cytoplasm and nucleus of dopaminergic neuron.