目的 探讨橄榄苦苷对脑缺血-再灌注（cerebral ischemia-reperfusion，CI/R）大鼠神经损伤及腺苷酸活化 蛋白激酶/沉默信息调节因子 2 相关酶 1/过氧化物酶体增殖物激活受体 γ 共激活因子 1α（AMPK/SIRT1/PGC-1α） 信号通路的影响。方法 构建 CI/R 大鼠模型，将造模成功大鼠随机分为模型组、橄榄苦苷低剂量组、橄榄苦 苷高剂量组、通路抑制剂组，每组 18 只，在造模成功即日进行灌胃药物，每日 1 次，连续给药 14 d。另取 18 只作为正常对照组。进行神经行为学评分；ELISA 法检测氧化应激水平；HE 染色法检测脑组织病理损伤； TTC 染色法检测脑梗死体积；TUNEL 染色法检测神经元凋亡情况；Western Blot 法检测 AMPK/SIRT1/PGC-1α 信号通路相关蛋白表达。结果 模型组较对照组神经元细胞排列紊乱，神经元数量减少，出现坏死现象，核 固缩深染，且周围空泡化严重，神经行为学评分、脑梗死体积、ROS、MDA 水平及细胞凋亡率、C-Caspase-3、 Caspase-3、Bax 表达升高（P＜0.05），SOD 活性、Bcl-2、p-AMPK/AMPK、SIRT1、PGC-1α 表达降低（P＜ 0.05）；橄榄苦苷低、高剂量组及通路抑制剂组较模型组神经元排列相对整齐，数量少量减少，伴随小面积坏 死及轻微核固缩现象，神经行为学评分、脑梗死体积、ROS、MDA 水平及细胞凋亡率、C-Caspase-3、 Caspase-3、Bax 表达降低（P＜0.05），SOD 活性、Bcl-2、p-AMPK/AMPK、SIRT1、PGC-1α 表达升高（P＜ 0.05）；通路抑制剂组较橄榄苦苷高剂量组神经元细胞病理损伤严重，神经元凋亡、坏死及核固缩现象加剧， 神经行为学评分、脑梗死体积、ROS、MDA 水平及细胞凋亡率、C-Caspase-3、Caspase-3、Bax 表达升高（P＜ 0.05），SOD 活性、Bcl-2、p-AMPK/AMPK、SIRT1、PGC-1α 表达降低（P＜0.05）。结论 橄榄苦苷可缓解 CI/R 大鼠的神经损伤，其作用机制与激活 AMPK/SIRT1/PGC1α 信号通路有关。

Objective To investigate the effect of oleuropein on neuroinjury and the AMPK/SIRT1/PGC-1α signaling pathway in rats with cerebral ischemia-reperfusion （CI/R）. Methods A CI/R rat model was established. Successfully modeled rats were randomly divided into four groups （n=18 per group）：the model group，the low-dose oleuropein group，the high-dose oleuropein group，and the pathway inhibitor group. Intragastric administration of the respective drugs began on the day of successful modeling，once daily for 14 consecutive days. An additional 18 rats served as the normal control group. Neurological deficit scores were assessed. Oxidative stress levels were measured by ELISA. Pathological damage to brain tissue was examined by hematoxylin-eosin （HE） staining. Cerebral infarct volume was determined by 2， 3， 5-triphenyltetrazolium chloride （TTC） staining. Neuronal apoptosis was detected by TUNEL staining. The protein expression levels of the AMPK/SIRT1/PGC-1α signaling pathway were measured by Western Blot. Results Compared with the control group，the model group exhibited disordered neuronal cell arrangement，reduced neuronal count， presence of necrosis， pyknotic and deeply stained nuclei， and severe perineuronal vacuolization. Neurological deficit scores，cerebral infarct volume，levels of ROS and MDA，the apoptosis rate，and the expression of C-Caspase-3，Caspase-3，and Bax were significantly increased （P＜0.05），while SOD activity and the expression of Bcl-2，p-AMPK/AMPK，SIRT1，and PGC-1α were decreased （P＜0.05）. Compared with the model group，the low-dose and high-dose oleuropein groups and the pathway inhibitor group showed relatively orderly neuronal arrangement，a small reduction in cell count，accompanied by small areas of necrosis and mild nuclear pyknosis. Their neurological deficit scores，cerebral infarct volume，levels of ROS and MDA，the apoptosis rate，and the expression of C-Caspase-3，Caspase-3，and Bax were decreased （P＜0.05），while SOD activity and the expression of Bcl-2， p-AMPK/AMPK，SIRT1，and PGC-1α were increased （P＜0.05）. Compared with the high-dose oleuropein group， the pathway inhibitor group exhibited more severe neuronal pathological damage， aggravated neuronal apoptosis， necrosis，and nuclear pyknosis，along with increased neurological deficit scores，cerebral infarct volume，levels of ROS and MDA，the apoptosis rate，and the expression of C-Caspase-3，Caspase-3，and Bax （P＜0.05），whereas SOD activity and the expression of Bcl-2， p-AMPK/AMPK， SIRT1， and PGC-1α were decreased （P＜0.05）. Conclusion Oleuropein can alleviate neuroinjury in CI/R rats，and its mechanism of action is related to the activation of the AMPK/SIRT1/PGC-1α signaling pathway.

R285.5

河北省医学科学研究课题计划项目（20240753）。