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贯叶金丝桃对大鼠脑缺血再灌注损伤的保护作用及机制研究
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王 宏 ，康 利，江 茜，刘伟伟，张 岩，傅 予（天津市医药科学研究所，天津 300020）
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中图分类号 R965 文献标志码 A 文章编号 1001-0408（2023）16-1961-06
DOI 10.6039/j.issn.1001-0408.2023.16.08
摘 要 目的 探讨贯叶金丝桃对大鼠脑缺血再灌注损伤的保护作用及潜在机制。方法 将雄性SD大鼠随机分为假手术组、模型
组、阳性对照组（尼莫地平0.012 g/kg）和贯叶金丝桃高、低剂量组（5.212、1.303 g/kg），每组10只。除假手术组外其余各组大鼠均
采用改良线栓法构建大鼠大脑左侧中动脉闭塞再灌注模型。各药物组大鼠于术后第2天开始灌胃相应药液，每天1次，连续7 d。
分别于药物干预前（造模后第1天）和末次给药后进行大鼠神经功能评分，以TTC染色法观察其末次给药后的脑梗死情况，以苏木
精-伊红染色法和TUNEL染色法分别观察其脑皮层、海马组织的病理改变和神经细胞的凋亡情况，以Western blot法和反转录聚
合酶链式反应法分别检测其促红细胞生成素（EPO）、促红细胞生成素受体（EPOR）、Janus激酶2（JAK2）、信号转导及转录激活因
子3（STAT3）、磷酸化STAT3（p-STAT3）蛋白和EPO、EPOR、JAK2、STAT3 mRNA的表达情况。结果 与假手术组比较，模型组大鼠
药物干预前、末次给药后的神经功能评分和脑梗死比例均显著升高（P＜0.01）；脑皮层和海马组织神经细胞受损明显，凋亡的神经
细胞明显增多，凋亡率显著升高（P＜0.01）；脑组织中 EPO、EPOR 蛋白及 mRNA 的表达水平均显著降低（P＜0.01），JAK2、p-
STAT3、STAT3蛋白和JAK2、STAT3 mRNA的表达水平均显著升高（P＜0.01）。与模型组比较，各药物组大鼠脑皮层和海马组织
神经细胞受损及凋亡情况均有所改善，各定量指标大部分显著好转（P＜0.05或P＜0.01）。结论 贯叶金丝桃对大鼠脑缺血再灌注
损伤具有保护作用，其机制可能与调节EPO介导的JAK2/STAT3信号通路有关。
关键词 贯叶金丝桃；脑缺血再灌注；促红细胞生成素；Janus激酶2/信号转导及转录激活因子3信号通路
Study on the protective effect of Hypericum perforatum on cerebral ischemia-reperfusion injury in rats and
its mechanism
WANG Hong， KANG Li， JIANG Qian， LIU Weiwei， ZHANG Yan， FU Yu（Tianjin Institute of Medical and
Pharmaceutical Science， Tianjin 300020， China）
ABSTRACT OBJECTIVE To study the protective effect and potential mechanism of Hypericum perforatum on cerebral ischemia-
reperfusion in rats. METHODS The male SD rats were randomly divided into sham operation group， model group， positive control
group （nimodipine 0.012 g/kg）， H. perforatum high-dose and low-dose groups （5.212， 1.303 g/kg）， with 10 rats in each group.
Except for sham operation group， the left middle cerebral artery ischemia-reperfusion model was established with the modified
suture method. Administration groups were given relevant medicine intragastrically since the second day after surgery， once a day，
for 7 consecutive days. The neurological function scores of rats were measured before drug intervention （the first day after
modeling） and after the last administration， and the cerebral infarction after the last administration was observed using TTC staining
method；HE staining and TUNEL staining methods were used to observe the pathological changes of the cerebral cortex and
hippocampus， and the apoptosis of nerve cells， respectively. Western blot and RT-PCR were used to observe the protein and mRNA
expressions of erythropoietin （EPO）， erythropoietin receptor （EPOR）， Janus kinase 2 （JAK2） and signal transduction and activator of
transcription 3 （STAT3）， and protein expression of phosphorylated STAT3 （p-STAT3）， respectively. RESULTS Compared with
sham operation group， neurological function score and the proportion of cerebral infarction in model group were significantly
increased before intervention and after the last administration （P＜0.01）， with significant damage to nerve cells in cerebral cortex
and hippocampus， an increase in apoptotic nerve cells， and a significant increase in apoptosis rate （P＜0.01）； protein and mRNA
expressions of EPO and EPOR in the brain tissue were significantly reduced （P＜0.01）， while the protein expressions of JAK2， p-
STAT3 and STAT3， and mRNA expressions of JAK2 and STAT3 were significantly increased （P＜0.01）. Compared with model
group， the damage and apoptosis of nerve cells in cerebral cortex and hippocampus of rats in administration groups were improved，
and the quantitative indicators were almost significantly improved （P＜0.05 or P＜0.01）. CONCLUSIONS H. perforatum has a
protective effect against cerebral ischemia-reperfusion injury in
Δ 基金项目 天津市卫生健康委员会、天津市中医药管理局中医
rats， and the related mechanism may be related to the
中西医结合科研课题（No.2019107）
＊第一作者 助理研究员，硕士。研究方向：心脑血管药理学。E- regulation of EPO-mediated JAK2/STAT3 signaling pathway.
mail：wh19860906@126.com KEYWORDS Hypericum perforatum； cerebral ischemia-
# 通信作者 副研究员，硕士。研究方向：天然药物提取与分析。 reperfusion； erythropoietin； Janus kinase 2/signal transduction
E-mail：fyyyyy_82@126.com and activator of transcription 3 signaling pathway
中国药房 2023年第34卷第16期 China Pharmacy 2023 Vol. 34 No. 16 · 1961 ·
