目的: 探讨TAK-242对脑卒中后抑郁大鼠海马炎症损伤的保护作用机制。方法: 将54只雄性3月龄SD大鼠分为假手术组18只、脑卒中后抑郁(PSD)模型组18只和TAK组18只,用线栓法建造大脑中动脉闭塞(MCAO)模型后进行3周慢性不可预见性应激(CUMS)刺激以建造PSD模型,PSD模型建造成功后,TAK组采用稀释后的TAK-242 0.3 mg/kg进行腹腔注射,分别在CUMS的第5天、10天、15天、20天分次进行。用酶联免疫吸附测定法检测外周血中IL-1β的水平。结果: 与假手术组相比,PSD组大鼠和TAK组大鼠的体质量、糖水偏好指数、移动情况(LA)均降低,IL-1β的水平显著增高(P＜0.05);与PSD组相比,TAK组大鼠的体质量、糖水偏好指数、LA均有所增加,IL-1β表达水平下降(P＜0.05)。结论: TAK-242可以通过抑制TLR4信号通路,降低外周血中IL-1β的表达水平,从而对脑卒中后抑郁大鼠海马炎症损伤发挥神经保护作用,同时可为临床防治脑卒中后抑郁提供新思路。
Objective: To investigate the protective mechanism of TAK-242 on hippocampal inflammatory injury in rats with post-stroke depression. Methods: A total of 54 male 3-month-old SD rats were divided into sham operation group (n=18), post-stroke depression (PSD) model group (n=18) and TAK group (n=18). The middle cerebral artery occlusion (MCAO) model was established by suture method, and then chronic unpredictable mild stress (CUMS) stimulation was performed for 3 weeks to establish the PSD model. After the PSD model was successfully established, the TAK group was intraperitoneally injected with diluted TAK-242 0.3 mg/kg, which was performed on the 5th, 10th, 15th and 20th day of CUMS, respectively. The level of IL-1β in peripheral blood was detected by enzyme-linked immunosorbent assay. Results: Compared with the sham operation group, the body weight, sucrose preference index and movement (LA) of the PSD group and the TAK group were lower than those of the sham operation group, and the level of IL-1β was significantly increased (P＜0.05). Compared with PSD group, the body weight, sucrose preference index and LA of rats in TAK group were increased, and the expression level of IL-1β was decreased (P＜0.05). Conclusion: TAK-242 can reduce the expression of IL-1β in peripheral blood by inhibiting TLR4 signaling pathway, thus exerting a neuroprotective effect on hippocampal inflammatory injury in rats with post-stroke depression, and providing new ideas for clinical prevention and treatment of post-stroke depression.
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