Qiu Zhi-Kun, He Jia-Li, Liu Xu, Zeng Jia, Chen Ji-Sheng, Nie Hong
College of Pharmacy, Jinan University, Guangzhou 510632, PR China; Pharmaceutical Department of the First Affiliated Hospital of Guangdong Pharmaceutical University, Clinical Pharmacy Department of Guangdong Pharmaceutical University, Guangzhou 510080, PR China.
Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, PR China.
J Ethnopharmacol. 2017 Feb 23;198:324-330. doi: 10.1016/j.jep.2016.12.028. Epub 2016 Dec 16.
Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder that is characterized by symptoms of re-experiencing, avoidance and hyperarousal, as well as social and professional dysfunction at least one month after the exposure to a traumatic event. Biosynthesis of allopregnanolone has been suggested as one of the important contributors to PTSD. Albiflorin (AF) extracted from Radix paeoniae Alba had been shown to be effective in the therapy of depression. However, few studies were concerned about the anti-PTSD-like effects of AF.
The current study aimed to evaluate the anti-PTSD-like effects of AF in an animal model and its possible mechanism.
To evaluate this, the single prolonged stress (SPS) model was used in the present study. The SPS rats were administered by AF (at doses of 3.5, 7 and 14.0mg/kg, i.g.) after induction of SPS from days 2-13. After the exposure to SPS, behavioral assessments were conducted, including contextual fear paradigm (CFP), elevated plus-maze test (EPMT), open-field test (OFT). The rats were decapitated at the end of the behavioral tests and levels of allopregnanolone in prefrontal cortex, hippocampus and amygdala were measured by enzyme linked immunosorbent assay (ELISA).
It had been shown that behavioral deficits of SPS rats were reversed by AF (7.0 and 14.0mg/kg, i.g.), which attenuated the PTSD-like associated contextual freezing behavior in CFP and improved PTSD-like associated anxiogenic behavior in EPMT without affecting locomotor activity in OFT. Moreover, decreased levels of allopregnanolone in prefrontal cortex, hippocampus, and amygdala were reversed by AF (7.0 and 14.0mg/kg, i.g.), respectively.
In summary, the present study indicated that AF exerted the anti-PTSD-like effects, which maybe associated with allopregnanolone biosynthesis in the brain.
创伤后应激障碍(PTSD)是一种严重的精神疾病,其特征为再次体验、回避和过度觉醒症状,以及在暴露于创伤事件后至少一个月出现社会和职业功能障碍。孕烷醇酮的生物合成被认为是PTSD的重要促成因素之一。从白芍中提取的芍药苷(AF)已被证明对抑郁症治疗有效。然而,很少有研究关注AF的抗PTSD样作用。
本研究旨在评估AF在动物模型中的抗PTSD样作用及其可能机制。
为评估此作用,本研究采用单次延长应激(SPS)模型。在第2至13天诱导SPS后,对SPS大鼠给予AF(剂量为3.5、7和14.0mg/kg,腹腔注射)。暴露于SPS后,进行行为评估,包括情境恐惧范式(CFP)、高架十字迷宫试验(EPMT)、旷场试验(OFT)。行为测试结束时将大鼠断头,通过酶联免疫吸附测定(ELISA)测量前额叶皮质、海马和杏仁核中孕烷醇酮的水平。
结果表明,AF(7.0和14.0mg/kg,腹腔注射)可逆转SPS大鼠的行为缺陷,减轻CFP中与PTSD样相关的情境性僵住行为,并改善EPMT中与PTSD样相关的焦虑行为,而不影响OFT中的运动活动。此外,AF(7.0和14.0mg/kg,腹腔注射)分别逆转了前额叶皮质、海马和杏仁核中孕烷醇酮水平的降低。
总之,本研究表明AF具有抗PTSD样作用,这可能与大脑中孕烷醇酮的生物合成有关。