成熟大鼠齿状回诱导NO合成酶表达模型抑郁的免疫表型特征及其药理纠正

A. Smirnov, M. Ekova, I. Tyurenkov, E. Volotova
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摘要

目的:研究成年大鼠抑郁模型时齿状回诱导NO合成酶(iNOS)的表达情况,并建立Phenibut及实验室编码RSPU-189、RSPU-135的化合物对iNOS表达变化的药理学纠正可能性。材料与方法:在持续7天(每天30分钟)的环境温度波动和持续限制活动的同时,结合高声、脉冲强光、振动等应激刺激,模拟动物的抑郁样行为。通过计算免疫反应物质的相对面积(IRM)和0 ~ 3点的染色强度来评估齿状回iNOS表达水平的变化。结果:与对照组相比,实验性抑郁大鼠齿状回颗粒层神经元核周细胞质中iNOS-IRM表达增加,神经元和神经细胞中iNOS-IRM相对面积增加。化合物RSPU-189 (salifen)的使用更大程度上显示了矫正效果,因为在大鼠齿状回颗粒层神经元核周细胞质中,iNOS-IRM的表达减少,神经细胞和神经细胞中iNOS-IRM的相对面积减少,这与对照组动物的这些参数值相对应。结论:成熟大鼠齿状回抑郁的实验模型显示,iNOS-IRM表达增加,而化合物RSPU-189(沙利芬)对其进行药理学校正后,iNOS-IRM表达降低,这可能表明该化合物对gaba能神经传递机制具有主要的神经保护作用。
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Immunophenotypic characteristics of inducible NO synthase expression in dentate gyrus of mature rats in modeling depression and its pharmacological correction
AIM: The work aimed to investigate inducible NO synthase (iNOS) expression in dentate gyrus in mature rats when modeling depression, as well as the establish the pharmacological correction possibility of detected changes with Phenibut and compounds under laboratory codes of RSPU-189, RSPU-135. MATERIALS AND METHODS: Depressive-like behavior in animals was modeled by combining stressful stimuli such as loud sound, pulsating bright light, and vibration simultaneous with constant restriction of mobility and fluctuations in temperature of environment for 7 days (daily for 30 minutes). Changes in level of iNOS expression in dentate gyrus were assessed by calculating relative area of immunoreactive material (IRM) and staining intensity in points from 0 to 3. RESULTS: Compared with the control group, rats with experimental depression showed an increase in expression of iNOS-IRM in cytoplasm of neuronal perikarya in granular layer of dentate gyrus, as well as an increase in relative area of iNOS-IRM in neuropil and nerve cells. The use of the compound RSPU-189 (salifen) demonstrated to a greater extent the corrective effect, since in the cytoplasm of neuronal perikarya in granular layer of dentate gyrus of rats, there was a decrease in the expression of iNOS-IRM, as well as a decrease in the relative area of iNOS-IRM in neuropil and nerve cells, which corresponded to values of these parameters in the control group of animals. CONCLUSIONS: An experimental modeling of depression in dentate gyrus of mature rats revealed an increase of iNOS-IRM expression, the decrease of which was noted in its pharmacological correction with the compound RSPU-189 (salifen), which may indicate the predominant neuroprotective effect of this compound on GABAergic neurotransmission mechanisms.
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