Li Cheng-Gang, Xu Lu-Shan, Sun Liang, Xu Yu-Hao, Cao Xiang, Zhao Chen-Chen, Xia Sheng-Nan, Zhang Qing-Xiu, Xu Yun
Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, 210008, China.
Chin J Integr Med. 2025 Jan;31(1):28-38. doi: 10.1007/s11655-024-3903-5. Epub 2024 Oct 2.
To investigate the therapeutic effect of Xiangshao Granules (XSG) on post-stroke depression (PSD) and explore the underlying mechanisms.
Forty-three C57BL/6J mice were divided into 3 groups: sham (n=15), PSD+vehicle (n=14), and PSD+XSG (n=14) groups according to a random number table. The PSD models were constructed using chronic unpredictable mild stress (CUMS) after middle cerebral artery occlusion (MCAO). The sham group only experienced the same surgical operation, but without MACO and CUMS stimulation. The XSG group received XSG (60 mg/kg per day) by gavage for 4 weeks. The mice in the sham and vehicle groups were given the same volume of 0.9% saline at the same time. The body weight and behavior tests including open field test, sucrose preference test, tail suspension test, and elevated plus-maze test, were used to validate the PSD mouse model. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining were used to evaluate the anti-inflammatory effects of XSG. The potential molecular mechanisms were explored and verified through network pharmacology analysis, Nissl staining, Western blot, ELISA, and RT-qPCR, respectively.
The body weight and behavior tests showed that MCAO combined with CUMS successfully established the PSD models. XSG alleviated neuronal damage, reduced the expressions of pro-apoptotic proteins Caspase-3 and B-cell lymphoma-2 (BCL-2)-associated X (BAX), and increased the expression of anti-apoptotic protein BCL-2 in PSD mice (P<0.05 or P<0.01). XSG inhibited microglial activation and the expressions of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1 β, and IL-6 via the toll-like receptor 4/nuclear factor kappa-B signaling pathway in PSD mice (P<0.05 or P<0.01). Furthermore, XSG decreased the expression of indoleamine 2,3-dioxygenase1 (IDO1) and increased the concentration of 5-hydroxytryptamine in PSD mice (P<0.05 or P<0.01).
XSG could reverse the anxiety/depressionlike behaviors and reduce the neuronal injury in the hippocampus and prefrontal cortex of PSD mice, which may be a potential therapeutic agent for PSD.
探讨香芍颗粒（XSG）对脑卒中后抑郁（PSD）的治疗作用并探究其潜在机制。
将43只C57BL/6J小鼠按随机数字表法分为3组：假手术组（n = 15）、PSD+溶媒组（n = 14）和PSD+XSG组（n = 14）。采用大脑中动脉闭塞（MCAO）后慢性不可预测性温和应激（CUMS）构建PSD模型。假手术组仅经历相同手术操作，但无MCAO和CUMS刺激。XSG组每天灌胃给予XSG（60 mg/kg），持续4周。假手术组和溶媒组小鼠同时给予相同体积的0.9%生理盐水。通过体重及行为学测试包括旷场试验、蔗糖偏好试验、悬尾试验和高架十字迷宫试验来验证PSD小鼠模型。采用实时荧光定量聚合酶链反应（RT-qPCR）、酶联免疫吸附测定（ELISA）和免疫荧光染色来评估XSG的抗炎作用。分别通过网络药理学分析、尼氏染色、蛋白质免疫印迹法（Western blot）、ELISA和RT-qPCR探究并验证潜在分子机制。
体重及行为学测试表明，MCAO联合CUMS成功构建了PSD模型。XSG减轻了PSD小鼠的神经元损伤，降低促凋亡蛋白半胱天冬酶-3（Caspase-3）和B细胞淋巴瘤-2（BCL-2）相关X蛋白（BAX）的表达，并增加抗凋亡蛋白BCL-2的表达（P<0.05或P<0.01）。XSG通过Toll样受体4/核因子κB信号通路抑制PSD小鼠小胶质细胞活化及肿瘤坏死因子-α、白细胞介素（IL）-1β和IL-6等促炎细胞因子的表达（P<0.05或P<0.01）。此外，XSG降低了PSD小鼠吲哚胺2,3-双加氧酶1（IDO1）的表达并增加了5-羟色胺的浓度（P<0.05或P<0.01）。
XSG可逆转PSD小鼠的焦虑/抑郁样行为，减轻海马和前额叶皮质的神经元损伤，可能是一种治疗PSD的潜在药物。
