Haghdoost-Yazdi Hashem, Piri Hossein, Faraji Ayda, Fraidouni Negin, Dargahi Tahereh, Mahmudi Marzieh, Alipour Heidari Mahmud
a Cellular and Molecular Research Center , Qazvin University of Medical Sciences , Qazvin , Iran.
Neurol Res. 2016 Apr;38(4):294-300. doi: 10.1080/01616412.2015.1114290. Epub 2016 Apr 21.
Potassium channels participate in cellular and molecular signalling pathways regulating the life and death of neurons. In this study, effect of pretreatment with potassium channel blockers of 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on the behavioural symptoms of 6-hydroxydopamine (6-OHDA)-induced Parkinsonism was evaluated.
6-OHDA was injected into right striatum of adult male Wistar rats using stereotaxic surgery. Severity of 6-OHDA-induced Parkinsonism was assessed by conventional behavioural tests. 4-AP and TEA were injected twice per day intraperitoneally, before 6-OHDA injection to 15 days after that. Also, malondialdehyde (MDA) concentration as a marker of oxidative stress was measured in rat sera.
Pretreatment with 4-AP (0.5 and 1 mg/kg) and TEA (2 and 5 mg/kg) attenuated significantly behavioural symptoms of 6-OHDA-induced Parkinsonism. Application of both 4-AP and TEA together was more effective than the effect of each one of these blockers alone. 6-OHDA increased MDA concentration but pretreatment with 4-AP prevented of 6-OHDA-induced increase in MDA. On the other hand, pretreatment with TEA and combination of TEA and 4-AP could not prevent of 6-OHDA-induced oxidative stress.
Since severity of behavioural symptoms of 6-OHDA-induced Parkinsonism is correlated to the degree of nigral dopaminergic cell death, we suggest that antiparkinsonism effect of TEA and 4-AP was mediated by their neuroprotective effect. Because, both Parkinsonism in rat and PD in human, the main pathophysiological hallmark, is neurodegeneration of dopaminergic neurons in substantia nigra, we suggest doing clinical trials for evaluation of effectiveness of 4-AP and TEA in slowing down of PD progress.
钾通道参与调节神经元生死的细胞和分子信号通路。在本研究中，评估了用钾通道阻滞剂4-氨基吡啶（4-AP）和四乙铵（TEA）预处理对6-羟基多巴胺（6-OHDA）诱导的帕金森病行为症状的影响。
采用立体定向手术将6-OHDA注入成年雄性Wistar大鼠的右侧纹状体。通过传统行为测试评估6-OHDA诱导的帕金森病的严重程度。在6-OHDA注射前至注射后15天，每天腹腔注射4-AP和TEA两次。此外，还测量了大鼠血清中作为氧化应激标志物的丙二醛（MDA）浓度。
用4-AP（0.5和1mg/kg）和TEA（2和5mg/kg）预处理可显著减轻6-OHDA诱导的帕金森病的行为症状。4-AP和TEA联合应用比单独使用这两种阻滞剂中的任何一种更有效。6-OHDA增加了MDA浓度，但用4-AP预处理可防止6-OHDA诱导的MDA增加。另一方面，用TEA预处理以及TEA和4-AP联合使用不能防止6-OHDA诱导的氧化应激。
由于6-OHDA诱导的帕金森病行为症状的严重程度与黑质多巴胺能细胞死亡程度相关，我们认为TEA和4-AP的抗帕金森病作用是由它们的神经保护作用介导的。因为大鼠帕金森病和人类帕金森病的主要病理生理标志都是黑质多巴胺能神经元的神经变性，我们建议进行临床试验以评估4-AP和TEA在减缓帕金森病进展方面的有效性。
