目的 探讨丹参保心茶 （Danshen Baoxin Cha） 对冠心病合并认知功能障碍大鼠的影响。方法 将雄性 SD大鼠随机分为正常组和模型复制组。模型复制组大鼠双侧脑室注射链脲佐菌素 （STZ） 造认知功能障碍模型，皮下注射盐酸异丙肾上腺素 （ISO） 造心肌缺血模型。通过行为学实验验证心肌缺血模型及认知功能障碍造模成功后，将模型复制组大鼠随机分为模型组、通心络胶囊组 （1.6 g•kg-1） 及丹参保心茶低 （4 g•kg-1） 、中 （8 g•kg-1） 、高 （16 g•kg-1） 剂量组，连续给药 2 周。采用 Y 迷宫、新物体识别实验、Morris 水迷宫实验检测大鼠的学习和记忆能力；采用试剂盒检测大鼠脑内氧化应激水平和线粒体中三磷酸腺苷 （ATP） 含量；采用苏木精-伊红 （HE） 染色法和 Nissl 染色法观察海马 CA1 区神经元的病理变化；采用电镜观察海马 CA1 区线粒体的病理变化；通过实时荧光定量 PCR 法检测过氧化物酶体增生物激活受体 γ 共激活因子 1α（PGC-1α）、葡萄糖转运蛋白4（GLUT4） 、视神经萎缩蛋白 1 （OPA1） 的表达水平；通过 Western Blot 检测 AMPK/OPA1 信号通路相关蛋白的表达量。结果 与正常组比，模型组自主交替率、识别指数、穿越原平台区域的次数和路程比明显降低 （P＜0.01） ；海马 CA1 区神经元密度下降，尼氏小体减少，胞核固缩增加；线粒体中 ATP 和脑组织中 ATP、SOD、GSH-PX 水平明显降低 （P＜0.05，P＜0.01） ，ROS、MDA 含量明显增加 （P＜0.05，P＜0.01） ；海马 CA1 区线粒体肿胀，嵴稀疏，呈空泡化；GLUT4、PGC-1α、OPA1 mRNA 表达水平均明显降低（P＜0.01）；GLUT4、SIRT1、PGC-1α、OPA1 的蛋白表达水平和 p-AMPK/AMPK 比值明显降低 （P＜0.05，P＜0.01） 。与模型组比，丹参保心茶给药组大鼠的行为学指标明显改善 （P＜0.05，P＜0.01） ，海马 CA1 区神经元数量、尼氏小体、核固缩改善；线粒体中 ATP 和脑组织中 ATP、SOD、GSH-PX 水平明显升高 （P＜0.05，P＜0.01） ，ROS、MDA 水平明显降低 （P＜0.05，P＜0.01） ；海马 CA1 区线粒体嵴结构较完整；GLUT4、PGC-1α、OPA1 mRNA 表达水平 改善 （P＜0.05，P＜0.01） ；AMPK/OPA1 信号通路相关蛋白表达量明显升高 （P＜0.05，P＜0.01） 。结论 丹参保心茶可以改善冠心病合并认知功能障碍模型大鼠的学习、记忆能力，减轻神经元损伤，其机制可能与减轻脑部氧化应激损伤，激活 AMPK/OPA1 信号通路，恢复能量水平有关。

Objective To investigate the effect of Danshen Baoxin Cha （DBC） on a rat model of coronary heart disease combined with cognitive impairment. Methods Male Sprague-Dawley（SD） rats were randomly assigned to two groups：normal group and model group. Streptozotocin was injected into the bilateral ventricles of rats in the model group to establish cognitive impairment model，then isoproterenol hydrochloride was injected subcutaneously to model myocardial ischemia. Behavioral experiments were conducted to verify the success of the model of cognitive dysfunction. The rats of the model group were randomly divided into five groups：model control group，Tongxinluo Capsule group （TXL group，1.6 g•kg-1），and low- （4 g•kg-1），medium- （8 g•kg-1），and high- （16 g•kg-1）dose DBC groups. These groups were received the respective treatments continuously for two weeks. Subsequently，the Y-maze，novel object recognition and Morris water maze experiment were employed to assess the learning and memory abilities of rats. A kit was utilized to quantify the level of oxidative stress in the brain and the adenosine triphosphate （ATP） content in the brain and mitochondria. Hematoxylin-eosin （HE） staining and Nissl staining were employed to observe the pathological changes of neurons in hippocampus CA1 region. Electron microscopy was utilized to observe the pathological changes of mitochondria in hippocampal CA1 region. The expression levels of peroxisome proliferator-activated receptor γ coactivator-1α（PGC-1α），glucose transporter type 4（GLUT4），and optic atrophy 1（OPA1） were quantified by real-time fluorescence quantitative polymerase chain reaction （PCR），and the expression of proteins related to the AMPK/OPA1 signaling pathway was determined by Western Blot analysis. Results Compared with the normal group， the spontaneous alternating reaction rate， the novel object recognition index，number of crossing the original platform，and distance ratio in the model group were obviously decreased （P＜0.01）. Neuronal density in the CA1 region of the hippocampus was decreased，Nissl bodies were decreased，and nucleus consolidation was increased. The ATP level in mitochondria，and the levels of ATP，SOD，and GSH-PX in brain were significantly decreased （P＜0.05，P＜0.01），as well as the content of ROS and MDA were significantly increased （P＜0.05，P＜0.01）. The mitochondria of hippocampus in CA1 region were swollen，with sparse and vacuolated cristae. The mRNA expression levels of GLUT4，PGC-1α，and OPA1 were significantly decreased （P＜0.01）. The protein expression levels of GLUT4，SIRT1，PGC-1α and OPA1，and p-AMPK/AMPK ratio were significantly decreased （P＜0.05，P＜0.01）. Compared with the model group，the behavioral indexes of rats in the DBC groups were significantly improved （P＜0.05，P＜0.01），the number of neurons in the hippocampal CA1 area，Nissl bodies and nucleus consolidation were improved. The ATP level in mitochondria and the levels of ATP，SOD，and GSH-PX in brain were significantly increased （P＜0.05，P＜0.01）. The levels of ROS and MDA were significantly decreased （P＜0.05， P＜0.01）. The structure of mitochondrial cristae in hippocampal CA1 region were relatively intact. The mRNA expression levels of GLUT4，PGC-1α and OPA1 were increased （P＜0.05，P＜0.01），and the expression of proteins related to the AMPK/OPA1 signaling pathway was significantly increased（P＜0.05，P＜0.01）. Conclusion DBC can enhance learning and memory abilities，reduce neuronal damage in a rat model of coronary heart disease combined with cognitive impairment. The mechanism may be related to the reduction of oxidative stress damage in the brain，the activation of the AMPK/OPA1 signaling pathway，and the restoration of energy levels.

R285.5

国家自然科学基金项目 （82074505，82374547）；广东省自然科学基金面上项目 （2023A1515011835）；广东省普通高校重点领域专项项目 （2022ZDZX2078）；广东省中医药局科研项目 （20231246）。