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帕立骨化醇在戊四氮诱导的大鼠癫痫模型中的抑制作用

Inhibitor effect of paricalcitol in rat model of pentylenetetrazol-induced seizures.

作者信息

Uyanıkgil Yiğit, Solmaz Volkan, Çavuşoğlu Türker, Çınar Bilge Piri, Çetin Emel Öykü, Sur Halil Yılmaz, Erbaş Oytun

机构信息

Department of Histology and Embryology, Ege University School of Medicine, Izmir, Turkey.

Cord Blood, Cell-Tissue Application and Research Center, Ege University, Izmir, Turkey.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2016 Oct;389(10):1117-22. doi: 10.1007/s00210-016-1273-z. Epub 2016 Jul 20.

Abstract

Vitamin D has various systemic effects on bone metabolism, modulation of the immune system, stabilization of the cell membrane, oxidative stress, inflammation, apoptosis, and various other hormones. Differing from active vitamin D, paricalcitol is a relatively safe VDR agonist due to its relatively few side effects. This study has investigated the anticonvulsant effect of paricalcitol in convulsions induced by pentylenetetrazole (PTZ). 36 male Sprague-Dawley rats were divided randomly into two groups: 18 for EEG recording (PTZ 35 mg/kg) and 18 for behavioral studies (PTZ 70 mg/kg). Forty-five minutes before the PTZ injection, both groups of rats were given 5 and 10 μg/kg of paricalcitol i.p., respectively. Racine convulsion scores, first myoclonic jerk time, spike percentages, and antioxidant status were evaluated in the groups. Our results showed that the Racine's Convulsion Scale (RCS) score significantly dropped in the paricalcitol-treated group, analysis of the first myoclonic jerk (FMJ) latencies demonstrated a significantly longer latency in the paricalcitol-applied group, and spike percentages at EEG recordings significantly decreased with paricalcitol. Moreover, MDA levels were lower and SOD activity were higher in the 5 μg/kg paricalcitol group compared to the saline group; these results were more prominent in 10 μg/kg paricalcitol group. Our study has demonstrated that paricalcitol has protective effects on PTZ-induced convulsions. Based on the SOD and MDA levels in our study, these effects may result from the antioxidant characteristics of paricalcitol.

摘要

维生素D对骨代谢、免疫系统调节、细胞膜稳定、氧化应激、炎症、细胞凋亡及多种其他激素具有多种全身性作用。与活性维生素D不同,帕立骨化醇是一种相对安全的维生素D受体激动剂,因其副作用相对较少。本研究调查了帕立骨化醇对戊四氮(PTZ)诱导惊厥的抗惊厥作用。将36只雄性Sprague-Dawley大鼠随机分为两组:18只用于脑电图记录(PTZ 35mg/kg),18只用于行为学研究(PTZ 70mg/kg)。在注射PTZ前45分钟,两组大鼠分别腹腔注射5μg/kg和10μg/kg的帕立骨化醇。评估各组的Racine惊厥评分、首次肌阵挛抽搐时间、棘波百分比和抗氧化状态。我们的结果显示,帕立骨化醇治疗组的Racine惊厥量表(RCS)评分显著下降,首次肌阵挛抽搐(FMJ)潜伏期分析表明,帕立骨化醇应用组的潜伏期显著延长,脑电图记录中的棘波百分比随帕立骨化醇显著降低。此外,与生理盐水组相比,5μg/kg帕立骨化醇组的丙二醛(MDA)水平较低,超氧化物歧化酶(SOD)活性较高;这些结果在10μg/kg帕立骨化醇组中更为显著。我们的研究表明,帕立骨化醇对PTZ诱导的惊厥具有保护作用。基于我们研究中的SOD和MDA水平,这些作用可能源于帕立骨化醇的抗氧化特性。

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