Haghdoost-Yazdi Hashem, Piri Hossein, Najafipour Reza, Faraji Ayda, Fraidouni Negin, Dargahi Tahereh, Alipour Heidari Mahmud
Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.
Neurosciences (Riyadh). 2017 Jan;22(1):44-50. doi: 10.17712/nsj.2017.1.20160266.
To evaluate the effect of K+ channels inhibitors in treatment of parkinson`s disease (PD).
This prospective comparative study was conducted in the Qazvin University of Medical Sciences, Iran, from April 2015 to January 2016. Male rats (n=37) received intraperitoneal doses of TEA (2 and 5 mg/kg) or 4-AP (0.5 and 1 mg/kg) twice-daily, before a stereotactic injection of 6-hydroxydopamine (6-OHDA) for the following 7 days. The 6-OHDA was injected into right medial forebrain bundle (MFB) of the rat brains. Development and severity of PD were assessed using the apomorphine-induced rotational test, the elevated body swing test and rotarod tests. Concentration of malondialdehyde (MDA), a marker of oxidative stress, was measured in rat sera.
Tetraethylammonium and 4-AP significantly reduced the number of apomorphine-induced rotations and improved motor learning in the rotarod test at both doses. Administration of 4-AP and TEA together was more effective than single administration of either agent. Malondialdehyde measurement showed that pretreatment with TEA could not prevent 6-OHDA-induced oxidative stress.
Our results showed that pretreatment with TEA and 4-AP has a neuroprotective effect against 6-OHDA in dopaminergic neurons in the substantia nigra.
评估钾通道抑制剂对帕金森病（PD）的治疗效果。
这项前瞻性比较研究于2015年4月至2016年1月在伊朗加兹温医科大学进行。雄性大鼠（n = 37）在立体定向注射6-羟基多巴胺（6-OHDA）前7天，每天两次腹腔注射TEA（2和5mg/kg）或4-AP（0.5和1mg/kg）。将6-OHDA注入大鼠脑右侧内侧前脑束（MFB）。使用阿扑吗啡诱导的旋转试验、抬高身体摆动试验和转棒试验评估PD的发展和严重程度。测量大鼠血清中氧化应激标志物丙二醛（MDA）的浓度。
两种剂量的四乙铵和4-AP均显著减少了阿扑吗啡诱导的旋转次数，并改善了转棒试验中的运动学习能力。联合使用4-AP和TEA比单独使用任何一种药物更有效。丙二醛测量表明，TEA预处理不能预防6-OHDA诱导的氧化应激。
我们的结果表明，TEA和4-AP预处理对黑质多巴胺能神经元中的6-OHDA具有神经保护作用。
