中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (8): 693-701.doi: 10.3969/j.issn.1673-5374.2013.08.003

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

他达拉非可用于沙土鼠缺血大脑损伤多巴胺能神经元的治疗

  

  • 收稿日期:2012-12-10 修回日期:2013-01-30 出版日期:2013-03-15 发布日期:2013-03-15

Neuroprotective effects of tadalafil on gerbil dopaminergic neurons following cerebral ischemia

Kwang Taek Kim1, Kyung Jin Chung1, Han Sae Lee1, Il Gyu Ko2, Chang Ju Kim2, Yong Gil Na3, Khae Hawn Kim1   

  1. 1 Department of Urology, Gachon University Gil Medical Center, Gachon University, Incheon 405-760, Republic of Korea
    2 Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea
    3 Department of Urology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon 301-721, Republic of Korea
  • Received:2012-12-10 Revised:2013-01-30 Online:2013-03-15 Published:2013-03-15
  • Contact: Khae Hawn Kim, M.D., Ph.D., Associate professor, Department of Urology, Gachon University Gil Medical Center, Gachon University, 1198 Guwol-dong, Namdong-Gu, Incheon 405-760, Republic of Korea, kimcho99@gilhospital.com.
  • About author:Kwang Taek Kim☆, M.D., Associate professor.

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摘要：

他达拉非作为磷酸二酯酶-5长效抑制剂，可减轻脑缺血后认知缺损，但对多巴胺能神经元的作用如何？为探究该问题，我们观察了他达拉非对脑缺血后环磷鸟苷和多巴胺功能的影响。发现脑缺血后纹状体和黑质环磷鸟苷水平和多巴胺D2受体表达下降，而酪氨酸羟化酶表达上升。而0, 0.1, 1和10 mg/kg他达拉非的喂饲可剂量依赖性的逆转上述指标的变化。提示他达拉非可减轻脑缺血诱导的多巴胺能神经元的损伤。

关键词: 神经再生, 脑损伤, 脑缺血, 他达拉非, 磷酸二酯酶-5抑制剂, 多巴胺, 多巴胺D2受体, 环磷鸟苷, 基金资助文章, 图片文章

Abstract:

Impairment of dopamine function, which is known to have major effects on behaviors and cognition, is one of the main problems associated with cerebral ischemia. Tadalafil, a long-acting phosphodiesterase type-5 inhibitor, is known to ameliorate neurologic impairment induced by brain injury, but not in dopaminergic regions. We investigated the neuroprotective effects of treatment with tadalafil on cyclic guanosine monophosphate level and dopamine function following cerebral ischemia. Forty adult Mongolian gerbils were randomly and evenly divided into five groups (n = 8 in each group): Sham-operation group, cerebral ischemia-induced and 0, 0.1, 1, and 10 mg/kg tadalafil-treated groups, respectively. Tadalafil dissolved in distilled water was administered orally for 7 consecutive days, starting 1 day after surgery. Cyclic guanosine monophosphate assay and immunohistochemistry were performed for thyrosine hydroxylase expression and western blot analysis for dopamine D2 receptor expression. A decrease in cyclic guanosine monophosphate level following cerebral ischemia was found with an increase in thyrosine hydroxylase activity and a decrease in dopamine D2 receptor expression in the striatum and substantia nigra region. However, treatment with tadalafil increased cyclic guanosine monophosphate expression, suppressed thyrosine hydroxylase expression and increased dopamine D2 receptor expression in the striatum and substantia nigra region in a dose-dependent manner. Tadalafil might ameliorate cerebral ischemia-induced dopaminergic neuron injury. Therefore, tadalafil has the potential as a new neuroprotective treatment strategy for cerebral ischemic injury.

Key words: neural regeneration, brain injury, cerebral ischemia, Tadalafil, phosphodiesterase type-5 inhibitor, dopamine, dopamine D2 receptor, cyclic guanosine monophosphate, grants-supported paper, photographs-containing paper, neuroregneration