目的 探讨大黄酸（RHE）对脑缺血小鼠的神经保护作用，及其通过抑制Notch/核因子（NF）-κB信号通路减轻炎症反应和神经元凋亡的潜在机制。 方法 采用经典大脑中动脉闭塞（MCAO）法构建缺血性脑卒中小鼠模型。将小鼠随机分为5组，每组18只：假手术组（sham）、模型组（MCAO）、MCAO+依达拉奉组（Eda）、MCAO+RHE、MCAO+RHE+Notch激活剂Jagged 1组（RHE+J）。采用Bederson评分系统、平衡木行走实验和加速旋转杆实验评估各组小鼠的神经功能和运动能力。2，3，5-三苯基氯化四氮唑（TTC）染色、HE染色、TUNEL法用于评估脑梗死、海马形态损伤和神经元凋亡。ELISA用于分析海马组织白细胞介素（IL)-6和肿瘤坏死因子（TNF)-α水平。Western blotting用于分析Caspase-3、Notch 1、Hes 1和NF-κB p65蛋白表达。 结果 与sham组相比，MCAO组Bederson评分、平衡木评分、脑梗死体积、IL-6和TNF-α水平、TUNEL阳性染色细胞比例、Caspase-3、Notch1、Hes1和p-NF-κB  p65蛋白表达均明显增加，而跌倒潜伏期明显降低（P<0.05）。与MCAO组相比，Eda组和RHE组Bederson评分、平衡木评分、脑梗死体积、IL-6和TNF-α水平、TUNEL阳性染色细胞比例、Caspase-3、Notch1、Hes1和p-NF-κB p65蛋白表达均明显降低，而跌倒潜伏期明显增加（P<0.05）。与RHE组相比，RHE+J组Bederson评分、平衡木评分、脑梗死体积、IL-6和TNF-α水平、TUNEL阳性染色细胞比例、Caspase-3、Notch1、Hes1和p-NF-κB p65蛋白表达均明显增加，而跌倒潜伏期明显降低（P<0.05）。 结论 大黄酸通过抑制Notch/NF-κB信号通路活化，显著改善脑缺血小鼠神经功能损伤，提示其具有潜在的临床应用价值。 

Objective To investigate the neuroprotective effect of rhein（RHE）on ischemic mice and its potential mechanism of reducing inflammatory response and neuronal apoptosis by inhibiting Notch/nuclear factor(NF)-κB signaling pathway.

Methods The classical middle cerebral artery occlusion (MCAO) method  was used to construct ischemic stroke mouse models. The mice were randomly divided into 5 groups including the sham operation group (sham), the model group (MCAO), the MCAO+edaravone group (Eda), the MCAO+RHE-treated group (RHE), and the MCAO+RHE+Notch activitor Jagged 1 group (RHE+J). Each group has 18 mice. The Bederson scoring system, balance beam walking test and accelerated rotating rod test were used to assess the neurological function and locomotor ability of mice in each group. 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin eosin staining, and TUNEL method  were used to assess cerebral infarction, hippocampal morphological damage, and neuronal apoptosis. ELISA was used to analysis the levels of interleukin (IL)-6 and tumor necrosis factor α (TNF-α) in hippocampal tissue. Western blotting was used to analysis caspase-3, Notch1, Hes1, and NF-κB p65 protein expression.    Results Compared with the sham group, Bederson score, balance beam score, cerebral infarct volume, IL-6 and TNF-α levels, the proportion of TUNEL-positively stained cells, caspase-3, Notch1, Hes1, and p-NF-κB p65 protein expression were significantly increased in the MCAO group, whereas the latency to fall decreased significantly (P<0.05) . Compared with the MCAO group, Bederson score, balance beam score, cerebral infarct volume, IL-6 and TNF-α levels, proportion of TUNEL-positively stained cells, caspase-3, Notch1, Hes1, and p-NF-κB p65 protein expression were significantly lower in both Eda and RHE groups, whereas the latency to fall increased significantly (P<0.05). Compared with the RHE group, Bederson score, balance beam score, cerebral infarction volume, IL-6 and TNF-α levels, the proportion of TUNEL-positively stained cells, caspase-3, Notch1, Hes1, and p-NF-κB p65 protein expression increased significantly in the RHE+J group, whereas the latency to fall decreased significantly (P<0.05).   Conclusion Rhein can significantly improve nerve function in ischemic mice by inhibiting Notch/NF-κB signaling pathway activation, suggesting that rhein has potential clinical application value.