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

王宏; 康利; 江茜; 刘伟伟; 张岩; 傅予

doi:10.6039/j.issn.1001-0408.2023.16.08

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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

药学研究 | 更新时间：2023-08-24

- 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
- Study on the protective effect of Hypericum perforatum on cerebral ischemia-reperfusion injury in rats and its mechanism
- 中国药房 2023年34卷第16期页码：1961-1966
- 作者机构：
  
  天津市医药科学研究所，天津　300020
- 作者简介：
  
  助理研究员，硕士。研究方向：心脑血管药理学。E-mail：wh19860906@126.com
  副研究员，硕士。研究方向：天然药物提取与分析。E-mail：fyyyyy_82@126.com
- 基金信息：
  
  天津市卫生健康委员会、天津市中医药管理局中医中西医结合科研课题(2019107)
- DOI：10.6039/j.issn.1001-0408.2023.16.08
  中图分类号： R965
- 纸质出版日期：2023-08-30，
  
  收稿日期：2023-02-21，
  
  修回日期：2023-06-16，
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王宏,康利,江茜等.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 ^Δ[J].中国药房,2023,34(16):1961-1966.

WANG Hong,KANG Li,JIANG Qian,et al.Study on the protective effect of Hypericum perforatum on cerebral ischemia-reperfusion injury in rats and its mechanism[J].ZHONGGUO YAOFANG,2023,34(16):1961-1966.
王宏,康利,江茜等.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 ^Δ[J].中国药房,2023,34(16):1961-1966. DOI： 10.6039/j.issn.1001-0408.2023.16.08.

WANG Hong,KANG Li,JIANG Qian,et al.Study on the protective effect of Hypericum perforatum on cerebral ischemia-reperfusion injury in rats and its mechanism[J].ZHONGGUO YAOFANG,2023,34(16):1961-1966. 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（

＜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（

＜0.01）；脑组织中EPO、EPOR蛋白及mRNA的表达水平均显著降低（

＜0.01），JAK2、p-STAT3、STAT3蛋白和JAK2、STAT3 mRNA的表达水平均显著升高（

＜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（

＜0.05或

＜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。

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 （

＜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 （

＜0.01）； protein and mRNA expressions of EPO and EPOR in the brain tissue were significantly reduced （

＜0.01）， while the protein expressions of JAK2， p-STAT3 and STAT3， and mRNA expressions of JAK2 and STAT3 were significantly increased （

＜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 （

＜0.05 or

＜0.01）.

CONCLUSIONS

H. perforatum

has a protective effect against cerebral ischemia-reperfusion injury in rats， and the related mechanism may be related to the regulation of EPO-mediated JAK2/STAT3 signaling pathway.

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

Keywords

cerebral ischemia-reperfusionerythropoietinJanus kinase 2/signal transduction and activator of transcription 3 signaling pathway

references

GBD 2019 Stroke Collaborators. Global，regional，and national burden of stroke and its risk factors，1990-2019：a systematic analysis for the Global Burden of Disease Study 2019[J]. Lancet Neurol，2021，20（10）：795-820.

ZHAO Y F，ZHANG X J，CHEN X Y，et al. Neuronal injuries in cerebral infarction and ischemic stroke：from mechanisms to treatment：review[J]. Int J Mol Med，2022，49（2）：15.

国家药典委员会. 中华人民共和国药典：一部[M]. 2020年版.北京：中国医药科技出版社，2020：242.

贡联兵. 圣·约翰草提取物片（路优泰®）国内上市后临床应用评价[J]. 药品评价，2016，13（1）：46-49，52.

EATEMADNIA A，ANSARI S，ABEDI P，et al. The effect of Hypericum perforatum on postmenopausal symptoms and depression：a randomized controlled trial[J]. Complement Ther Med，2019，45：109-113.

VALVASSORI S S，BORGES C，BAVARESCO D V，et al. Hypericum perforatum chronic treatment affects cognitive parameters and brain neurotrophic factor levels[J]. Braz J Psychiatry，2018，40（4）：367-375.

USLUSOY F，NAZıROĞLU M，ÖVEY İ S，et al. Hypericum perforatum L. supplementation protects sciatic nerve injury-induced apoptotic，inflammatory and oxidative damage to muscle，blood and brain in rats[J]. J Pharm Pharmacol，2019，71（1）：83-92.

徐虹. 电针百会、足三里穴对脑缺血再灌注损伤大鼠EPO介导的JAK2/STAT3信号的影响[D]. 北京：北京协和医学院，2017.

YANG Y，HE B，ZHANG X C，et al. Geraniin protects against cerebral ischemia/reperfusion injury by suppres-sing oxidative stress and neuronal apoptosis via regulation of the Nrf2/HO-1 pathway [J]. Oxid Med Cell Longev，2022，2022：2152746.

BEDERSON J B，PITTS L H，TSUJI M，et al. Rat middle cerebral artery occlusion：evaluation of the model and development of a neurologic examination[J]. Stroke，1986，17（3）：472-476.

宋发萍，张洁，唐勇，等. 平肝活血散对大鼠脑缺血再灌注损伤的影响及作用机制初探[J]. 中国药房，2022，33（24）：2999-3004.

刘伟伟，聂卫，崔晓雪，等. 复方景川片对大鼠缺血性脑损伤的保护作用及对小胶质细胞/巨噬细胞极化的影响[J]. 天津医药，2021，49（8）：824-828.

DONG Y F，HU C Y，HUANG C X，et al. Interleukin-22 plays a protective role by regulating the JAK2-STAT3 pathway to improve inflammation，oxidative stress，and neuronal apoptosis following cerebral ischemia-reperfusion injury[J]. Mediators Inflamm，2021，2021：6621296.

FAN L C，ZHOU L C. Anti-IL-23 exerted protective effects on cerebral ischemia-reperfusion injury through JAK2/STAT3 signaling pathway[J]. Mol Biol Rep，2021，48（4）：3475-3484.

吕明义，邓淑玲，郭文晏，等. 木犀草素抑制JAK2/STAT3信号通路减轻大鼠脑缺血再灌注损伤作用的研究[J]. 天津医药，2022，50（4）：363-368.

TSIFTSOGLOU A S. Erythropoietin（EPO）as a key regulator of erythropoiesis，bone remodeling and endothelial transdifferentiation of multipotent mesenchymal stem cells（MSCs）：implications in regenerative medicine[J]. Cells，2021，10（8）：2140..

LIU F，LU Z，LI Z Y，et al. Electroacupuncture improves cerebral ischemic injury by enhancing the EPO-JAK2-STAT5 pathway in rats[J]. Neuropsychiatr Dis Treat，2021，17：2489-2498.

CHEN G，ZHANG S M，SHI J X，et al. Effects of recombinant human erythropoietin（rhEPO）on JAK2/STAT3 pathway and endothelial apoptosis in the rabbit basilar artery after subarachnoid hemorrhage[J]. Cytokine，2009，45（3）：162-168.

XU H，ZHANG Y M，SUN H，et al. Electroacupuncture at GV20 and ST36 exerts neuroprotective effects via the EPO-mediated JAK2/STAT3 pathway in cerebral ische-mic rats[J]. Evid Based Complement Alternat Med，2017，2017：6027421.

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