Herkinorin预处理减轻缺血性卒中模型大鼠脑损伤

doi:10.16352/j.issn.1001-6325.2023.03.456

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (3): 456-461.doi: 10.16352/j.issn.1001-6325.2023.03.456

Herkinorin预处理减轻缺血性卒中模型大鼠脑损伤

宋婉晴¹, 李俊发², 崔旭^1*

1.首都医科大学附属北京同仁医院麻醉科,北京 100730;
2.首都医科大学神经生物学系,北京 100069

收稿日期:2022-07-14 修回日期:2022-10-17 出版日期:2023-03-05 发布日期:2023-02-27
通讯作者: * cuixubjtr@ccmu.edu.cn
基金资助:
北京市自然科学基金 (7212019)

Herkinorin pretreatment alleviates cerebral injury in rat models with ischemic stroke

SONG Wanqing¹, LI Junfa², CUI Xu^1*

1. Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730;
2. Department of Neurobiology, Capital Medical University, Beijing 100069, China

Received:2022-07-14 Revised:2022-10-17 Online:2023-03-05 Published:2023-02-27
Contact: * cuixubjtr@ccmu.edu.cn

摘要/Abstract

摘要： 目的探讨Herkinorin预处理对短暂性大脑中动脉阻塞(tMCAO)大鼠脑组织NOD样受体蛋白3(NLRP3)的调节及作用机制。方法将大鼠随机分为假手术组(sham)、模型组(tMCAO)、Herkinorin组(Herkinorin),Herkinorin组大鼠造模前腹腔给予Herkinorin(10 mg/kg)1周,每天1次。再灌注24 h后对大鼠进行神经功能评分、TTC染色、TUNEL染色;Western blot检测IκBα、p65、p-p65、pro-IL-1β、IL-1β、pro-caspase1、caspase1 p20、NLRP3表达;免疫共沉淀(Co-IP)检测IκBα与β-抑制蛋白2(β-arrestin2)结合。结果与sham组相比,tMCAO组大鼠神经功能评分增加(P＜0.01),脑梗死百分比与脑水肿率增加(P＜0.01),脑组织缺血半影区中细胞凋亡水平增加(P＜0.01),IκBα、p65表达水平下降(P＜0.01),p-p65、IL-1β、caspase1 p20、NLRP3表达水平增加(P＜0.01),IκBα与β-arrestin2结合水平下降(P＜0.01);与tMCAO组相比,Herkinorin组大鼠神经功能评分下降(P＜0.01),脑梗死百分比与脑水肿率降低(P＜0.01),脑组织缺血半影区中细胞凋亡水平降低(P＜0.01),IκBα、p65表达水平增加(P＜0.01),p-p65、IL-1β、caspase1 p20、NLRP3表达水平降低(P＜0.01),IκBα与β-arrestin2结合水平增加(P＜0.01)。结论 Herkinorin可能通过抑制NF-κB/NLRP3通路减轻tMCAO大鼠脑缺血/再灌注损伤。

关键词: Herkinorin, 短暂性大脑中动脉阻塞, NOD样受体蛋白3, NF-κB, β-抑制蛋白2

Abstract: Objective To investigate the regulation and mechanism of Herkinorin preconditioning on NOD-like receptor protein 3 (NLRP3) in brain tissue of transient middle cerebral artery occlusion (tMCAO) rats. Methods Rats were randomly divided into sham operation group (sham), model group (tMCAO) and Herkinorin group (Herkinorin). Before modeling, rats in Herkinorin group were intraperitoneally given Herkinorin (10 mg/kg) once a day for a week. The rats were evaluated by neurologic score, TTC staining, TUNEL staining 24 h after reperfusion. The expression levels of IκBα, p65, p-p65, pro-IL-1β, IL-1β, pro-caspase1, caspase1 p20 and NLRP3 were detected by Western blot. The binding level of IκBα to β-arrestin2 was detected by co-immunoprecipitation (Co-IP). Results Compared with sham group, rats in tMCAO group had higher behavioral score (P＜0.01), increased cerebral infarction percentage and increased cerebral edema rate (P＜0.01). The level of cell apoptosis was increased in ischemic penumbra (P＜0.01). The expression levels of IκBα and p65 were decreased (P＜0.01) and the expression levels of p-p65, IL-1β, caspase1 p20 and NLRP3 were increased in ischemic penumbra (P＜0.01). The binding level of IκBα to β-arrestin2 was decreased in ischemic penumbra (P＜0.01). Compared with tMCAO group, rats in Herkinorin group had lower behavioral score (P＜0.01), lower cerebral infarction percentage and lower cerebral edema rate (P＜0.01). The level of cell apoptosis was decreased in ischemic penumbra(P＜0.01). The expression of IκBα and p65 was increased (P＜0.01) and the expression of p-p65, IL-1β, caspase1 p20 and NLRP3 was decreased in ischemic penumbra (P＜0.01). The binding of IκBα to β-arrestin2 was increased in ischemic penumbra (P＜0.01). Conclusions Herkinorin may negatively regulate NF-κB/NLRP3 pathway to alleviate cerebral ischemia-reperfusion injury of tMCAO rats.

Key words: Herkinorin, transient middle cerebral artery occlusion, NOD-like receptor protein 3, NF-κB, β-arrestin2

中图分类号:

R965

宋婉晴, 李俊发, 崔旭. Herkinorin预处理减轻缺血性卒中模型大鼠脑损伤[J]. 基础医学与临床, 2023, 43(3): 456-461.

SONG Wanqing, LI Junfa, CUI Xu. Herkinorin pretreatment alleviates cerebral injury in rat models with ischemic stroke[J]. Basic & Clinical Medicine, 2023, 43(3): 456-461.

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Herkinorin预处理减轻缺血性卒中模型大鼠脑损伤

Herkinorin pretreatment alleviates cerebral injury in rat models with ischemic stroke

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