Lopez-Real A, Rey P, Soto-Otero R, Mendez-Alvarez E, Labandeira-Garcia J L
Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
J Neurosci Res. 2005 Sep 15;81(6):865-73. doi: 10.1002/jnr.20598.
It is now established that the brain possesses a local renin-angiotensin system and that angiotensin II exerts multiple actions in the nervous system, including regulation of striatal dopamine release. Furthermore, angiotensin activates NADPH-dependent oxidases, which are a major source of superoxide, and angiotensin-converting enzyme inhibitors, commonly used in the treatment of hypertension and chronic heart failure, have shown antioxidant properties in several tissues. Oxidative stress is a key contributor to the pathogenesis and progression of Parkinson's disease. In the present study, we treated rats with intraventricular injections of the dopaminergic neurotoxin 6-hydroxydopamine and subcutaneous injections of the angiotensin-converting enzyme inhibitor Captopril to study the possible neuroprotective effect of the latter on the dopaminergic system and on 6-hydroxydopamine-induced oxidative stress. Rats treated with Captopril and 6-hydroxydopamine showed significantly less reduction in the number of dopaminergic neurons (i.e., immunoreactive to tyrosine hydroxylase) in the substantia nigra and in the density of striatal dopaminergic terminals than 6-hydroxydopamine-lesioned rats not treated with Captopril. In addition, Captopril reduced the levels of major oxidative stress indicators (i.e., lipid peroxidation and protein oxidation) in the ventral midbrain and the striatum of 6-hydroxydopamine-lesioned rats. Our results suggest that angiotensin-converting enzyme inhibitors may be useful for treatment of Parkinson's disease and that further investigation should focus on the neuroprotective capacity of these compounds.
现已证实，大脑拥有局部肾素 - 血管紧张素系统，且血管紧张素II在神经系统中发挥多种作用，包括调节纹状体多巴胺释放。此外，血管紧张素激活作为超氧化物主要来源的NADPH依赖性氧化酶，而常用于治疗高血压和慢性心力衰竭的血管紧张素转换酶抑制剂在多个组织中已显示出抗氧化特性。氧化应激是帕金森病发病机制和病情进展的关键因素。在本研究中，我们通过向大鼠脑室内注射多巴胺能神经毒素6 - 羟基多巴胺，并皮下注射血管紧张素转换酶抑制剂卡托普利，以研究后者对多巴胺能系统以及6 - 羟基多巴胺诱导的氧化应激可能具有的神经保护作用。与未用卡托普利治疗的6 - 羟基多巴胺损伤大鼠相比，用卡托普利和6 - 羟基多巴胺治疗的大鼠黑质中多巴胺能神经元数量（即对酪氨酸羟化酶免疫反应阳性）以及纹状体多巴胺能终末密度的减少明显较少。此外，卡托普利降低了6 - 羟基多巴胺损伤大鼠腹侧中脑和纹状体中主要氧化应激指标（即脂质过氧化和蛋白质氧化）的水平。我们的结果表明，血管紧张素转换酶抑制剂可能对帕金森病的治疗有用，并且进一步的研究应聚焦于这些化合物的神经保护能力。
