Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
Department of Basic Pathology, Federal University of Paraná, Curitiba, PR, Brazil.
Pharmacol Rep. 2019 Aug;71(4):556-564. doi: 10.1016/j.pharep.2018.11.005. Epub 2018 Nov 30.
Peroxisome proliferator-activated receptor γ (PPAR-γ) agonists have received much attention in research because of their neuroprotective and anti-inflammatory effects that reduce cell death and halt the progression of neurodegeneration. Thus, this study observed the pioglitazone effects on the main inflammatory markers after 6-hydroxydopamine (6-OHDA) lesion.
The effects of a 5-day administration of the PPAR-γ agonist pioglitazone (30 mg/kg) in male Wistar rats that received bilateral intranigral infusions of 6-OHDA. After surgery, the rats were evaluated in the open-field test on days 1,7,14, and 21. Immediately after the behavioral tests on day 21, the rats were euthanized, and the substantia nigra was removed to analyze the expression of nuclear factor κB (NF-κB) and IκB by western blot. To immunohistochemical, animals were intracardially perfused, with brain removal that was frozen and sectioned, being selected slices of the SNc region to detect tyrosine hydroxylase (TH) immunoreactivity, microglia activation (Iba-1) and NF-κB translocation in the nucleus.
Pioglitazone protected rats against hypolocomotion and 6-OHDA-induced dopaminergic neurodegeneration on day 7. Decreases in the microglial activation and the NF-κB expression were observed, and the p65 activation was inhibited.
These results suggest that pioglitazone may be a potential adjuvant for the treatment of Parkinson`s disease because of its effects on pathological markers of the progression of neurodegeneration.
过氧化物酶体增殖物激活受体 γ（PPAR-γ）激动剂因其具有神经保护和抗炎作用而受到广泛关注，这些作用可以减少细胞死亡并阻止神经退行性变的进展。因此，本研究观察了吡格列酮在 6-羟多巴胺（6-OHDA）损伤后对主要炎症标志物的影响。
将 PPAR-γ 激动剂吡格列酮（30mg/kg）连续 5 天给药，给予双侧纹状体注射 6-OHDA 的雄性 Wistar 大鼠。手术后，大鼠在第 1、7、14 和 21 天进行旷场测试。在第 21 天的行为测试后立即处死大鼠，取出黑质，通过 Western blot 分析核因子 κB（NF-κB）和 IκB 的表达。为了进行免疫组织化学，对动物进行心脏灌注，取出大脑进行冷冻切片，选择 SNc 区域的切片检测酪氨酸羟化酶（TH）免疫反应性、小胶质细胞激活（Iba-1）和 NF-κB 在核内的易位。
吡格列酮可预防大鼠在第 7 天出现运动减少和 6-OHDA 诱导的多巴胺能神经退行性变。观察到小胶质细胞激活和 NF-κB 表达减少，p65 激活受到抑制。
这些结果表明，吡格列酮可能是治疗帕金森病的潜在辅助药物，因为它可以影响神经退行性变进展的病理标志物。
