3-NP诱导大鼠纹状体损伤的组织病理学证实

The histopathological evidence of striatal injury induced by 3-NP in rats

目的探察证实3-NP对实验大鼠纹状体的损害作用。方法实验借助行为学探测、经典组化和免疫组化染色技术对大鼠运动行为学和纹状体组织病理学变化进行形态学探察,实验数据采用SPSS软件统计学处理。结果①运动行为学探测显示大鼠过平衡木的启动延搁时间和完成全过程时间明显延长(P<0.05,P<0.05),以及前爪滑落次数与3-NP处理之前比较具有统计学差异(P<0.05),其抓握时间也明显比3-NP处理之前延长(P<0.05)。②组织学探察显示,多种组化染色均在实验大鼠纹状体的背外侧区恒定出现一块明显的坏死灶,发生率为80%。坏死区及其周边区绝大部分神经元发生丢失,仅有少数体积较大的细胞幸存。Golgi染色显示在周边区幸存神经元的树突发生明显断裂和弯曲。酶组化显示病灶区SDH明显淡染,周边区可见一些强反应的细胞。③神经元特异性抗体探察显示坏死灶及其周边区神经元丢失严重,纹状体投射神经元的丢失更显著。对神经元死亡和损伤性质的进一步鉴定结果显示在坏死灶及其周边区均可见大量凋亡细胞。结论 3-NP特异性地诱导纹状体背外侧区神经元损伤,纹状体不同类型神经元对3-NP损伤显示不同的敏感性,凋亡和能量代谢障碍因素牵涉到此病理过程。

Objective To confirm the effect of motor behavior and striatal histology in rat after treated by 3-NP.Methods Behavioral testing,histochemical and immunohistochemical stainings were used to evaluate the changes of motor behavior and striatal histology,experimental data were analyzed by SPSS software.Results ① Behavioral testing showed that rats took longer time to initiate movement and complete the task in the balance-beam task（P0.05,P0.05）,and the footslips were significant compared with the control（P0.05）.The hang time was longer in the grip-strength task after treated by 3-NP（P0.05）.②Histochemical stains revealed that 80% of the experimental rats had a localized lesion in the dorsal striatum bilaterally.There was an obvious loss of neurons in the center and penumbra area of lesion,only few positive neurons with larger size were spared.Golgi stain showed that the dendrites of surviving neurons disrupted and bended obviously.Enzymohistochemical stain of SDH was hypochromatic in the center of lesion but some cells with strong reactivity appeared in the penumbra area.③Specific antibodies of neuronal stain were used,which showed that,compared between the total neurons and projection neurons,the latter lost more in the center and penumbra area of lesion.The further detect of neuronal death and the nature of injury displayed that a large number of apoptotic cells appeared in and around the lesion.Conclusion 3-NP specifically induce the neuronal injury in dorsolateral striatum;striatal neurons displayed different sensitivity to 3-NP induced injury;apoptosis and metabolic disorder were involved in the pathological process.