【摘要】 目的 探讨粒细胞集落刺激因子（G-CSF）在酒精使用障碍（AUD）合并缺血性脑卒中（IS）大鼠中的脑保护作用及作用机制。方法 采用随机数字表法将54只雄性Sprague Dawley大鼠分为AUD组、AUD+IS组和AUD+IS+G-CSF组，每组18只。3组大鼠均使用20%双瓶自由间歇性饮酒法建立AUD模型；AUD+IS组和AUD+IS+G-CSF组大鼠在AUD模型制备成功后采用线栓法制备IS模型；AUD+IS+G-CSF组大鼠在AUD模型与IS模型构建成功后2 h,腹腔注射G-CSF 50μg·kg^-1。每天记录所有大鼠的酒精摄入量及酒精偏好。在IS后24 h,对各组大鼠进行神经功能评分，使用氯化三苯基四氮唑对脑组织进行染色并计算脑梗死体积占比。采用末端脱氧核苷酸转移酶dUTP缺口末端标记法（TUNEL）检测脑组织阳性细胞率，酶联免疫吸附试验检测血清炎症因子白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）的水平。结果 AUD+IS组、AUD+IS+G-CSF组大鼠的神经功能评分显著高于AUD组（P<0.05）,AUD+IS+G-CSF组大鼠的神经功能评分显著低于AUD+IS组（P<0.05）;AUD+IS组、AUD+IS+G-CSF组大鼠脑梗死体积占比显著大于AUD组（P<0.05）,AUD+IS+G-CSF组大鼠的脑梗死体积占比显著小于AUD+IS组（P<0.05）。AUD+IS组、AUD+IS+G-CSF组大鼠脑组织TUNEL阳性细胞率显著高于AUD组（P<0.05）,AUD+IS+G-CSF组大鼠脑组织TUNEL阳性细胞率显著低于AUD+IS组（P<0.05）。AUD+IS组、 AUD+IS+G-CSF组大鼠血清中IL-6、TNF-α水平显著高于AUD组（P<0.05）;AUD+IS+G-CSF组大鼠血清IL-6、TNF-α水平显著低于AUD+IS组（P<0.05）。结论 G-CSF治疗可改善AUD合并IS大鼠的神经功能，可能与减少神经细胞凋亡、抑制炎症反应有关。更多还原

【Abstract】 Objective To investigate the brain-protective effect and mechanism of granulocyte colony-stimulating factor（G-CSF） in rats with alcohol use disorder（AUD） combined with ischemic stroke（IS）.Methods A total of 54 male Sprague Dawley rats were divided into the AUD group, AUD+IS group, and AUD+IS+G-CSF group using a random number table, with 18 rats in each group.The AUD model was established in all rats in the three groups using a 20% two-bottle free-choice intermittent drinking method.After the successful establishment of the AUD model, the IS model was established in the AUD+IS and AUD+IS+G-CSF groups using the suture occlusion method.Rats in the AUD+IS+G-CSF group received intraperitoneal injection of G-CSF(50 μg·kg^-1) at 2 hours after the successful establishment of both the AUD and IS models.The alcohol intake and preference of all rats were recorded daily.At 24 hours after IS,neurological function scores of rats in each group were assessed, and the proportion of cerebral infarction volumes were calculated after staining brain tissues with triphenyl tetrazolium chloride.The positive cell rate of brain tissues was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling（TUNEL）.Serum levels of inflammatory cytokines like interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α） were measured by using enzyme-linked immunosorbent assay.Results Neurological function scores of rats in the AUD+IS and AUD+IS+G-CSF groups were significantly higher than those in the AUD group（P<0.05）,while the neurological function score of rats in the AUD+IS+G-CSF group was significantly lower than that in the AUD+IS group（P<0.05）.Proportion of cerebral infarction volumes of rats in the AUD+IS and AUD+IS+G-CSF groups were significantly larger than those in the AUD group（P<0.05）,while the proportion of cerebral infarction volume of rats in the AUD+IS+G-CSF group was significantly smaller than that in the AUD+IS group（P<0.05）.The TUNEL-positive cell rate in brain tissues of rats was significantly higher in the AUD+IS and AUD+IS+G-CSF groups compared to the AUD group（P<0.05）,but significantly lower in the AUD+IS+G-CSF group compared to the AUD+IS group（P<0.05）.Serum levels of IL-6 and TNF-α were significantly elevated in the AUD+IS and AUD+IS+G-CSF groups compared to the AUD group（P<0.05）;however, serum levels of IL-6 and TNF-α in the AUD+IS+G-CSF group were significantly lower than those in the AUD+IS group（P<0.05）.Conclusion G-CSF treatment can improve neurological function in rats with AUD and IS,which may be related to the reduction of neuronal apoptosis and the inhibition of inflammatory responses.更多还原