Department of Encephalopathy, Affiliated hospital of Shaanxi University of Chinese Medicine, West Weiyang Road, Xianyang 712000, China.
J Tradit Chin Med. 2019 Oct;39(5):658-666.
To identify the antidepressant effect of Xingnao Jieyu (XNJY) decoction on a post-stroke depression (PSD) rat model and the underlying molecular mechanism.
We established a rat PSD model by middle cerebral artery occlusion (MCAO) combined with chronic unpredictable mild stress (CUMS). Healthy SD rats were randomly divided into six groups: sham, PSD, fluoxetine (Flu), and XNJY groups at low, middle, and high doses. The sham group underwent sham operation, while the other groups underwent MCAO+CUMS. The Flu and XNJY decoction groups were intragastrically administered with Flu or different doses of XNJY for 21 consecutive days. Histopathological changes in the cortex and hippocampus were observed by staining with hematoxylin and eosin and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling. Iba1 positive cells were evaluated by immunofluorescence assay. The expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in the cortex and hippocampus were measured by enzyme linked immunosorbent assay.
The PSD group rats had a significant decrease in body weight, consumption of sucrose water, and locomotor activity but an increase in immobility time during a forced swimming test (P < 0.01) compared with sham group. Flu and different doses of XNJY significantly recovered these indices (P < 0.01). XNJY also inhibited neuronal damage and apoptosis in the cortex induced by PSD (P < 0.01). Furthermore, XNJY reduced the number of Iba1 positive cells and the expressions of TNF-α, IL-6, and IL-1β, in addition to recovered the levels of 5-HT and NE in the cortex and hippocampus (P < 0.01).
The alleviation of neuroinflammation might be an important mechanism of the XNJY decoction against PSD. Thus, XNJY might be a promising candidate for the treatment of PSD.
探讨醒脑解郁汤对脑卒中后抑郁（PSD）大鼠模型的抗抑郁作用及其潜在的分子机制。
采用大脑中动脉闭塞（MCAO）结合慢性不可预测轻度应激（CUMS）建立 PSD 大鼠模型。将健康 SD 大鼠随机分为 6 组：假手术组、PSD 组、氟西汀（Flu）组和醒脑解郁汤低、中、高剂量组。假手术组仅接受假手术，其余各组均行 MCAO+CUMS。Flu 组和醒脑解郁汤组连续 21 天分别灌胃给予 Flu 和不同剂量的醒脑解郁汤。苏木精-伊红（HE）和末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）染色观察皮质和海马组织病理学变化。免疫荧光法检测小胶质细胞标志物 Iba1 阳性细胞的表达。酶联免疫吸附试验（ELISA）检测皮质和海马组织中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、5-羟色胺（5-HT）和去甲肾上腺素（NE）的表达。
与假手术组相比，PSD 组大鼠的体重、糖水消耗量和旷场实验中的运动活性明显下降，但强迫游泳试验中的不动时间明显增加（P<0.01）。Flu 和不同剂量的醒脑解郁汤均可显著恢复上述指标（P<0.01）。醒脑解郁汤还可抑制 PSD 诱导的皮质神经元损伤和凋亡（P<0.01）。此外，醒脑解郁汤还可减少 Iba1 阳性细胞的数量以及 TNF-α、IL-6 和 IL-1β的表达，并恢复皮质和海马组织中 5-HT 和 NE 的水平（P<0.01）。
减轻神经炎症可能是醒脑解郁汤治疗 PSD 的重要机制之一。因此，醒脑解郁汤可能是治疗 PSD 的一种有前途的候选药物。
