橙皮苷抑制HMGB1/NLRP3轴对七氟醚诱导的新生大鼠的神经保护作用研究  

Neuroprotective effect of hesperidin on sevoflurane-induced neonatal rats by inhibiting HMGB1/NLRP3 axis

作　　者：张贵星 祁星 曹雪 刘毅 吕靖 曾文静[1] ZHANG Guixing;QI Xing;CAO Xue;LIU Yi;LYU Jing;ZENG Wenjing(Anesthesia,Taihe Hospital Affiliated Hospital of Hubei University of Medicine,Shiyan,Hubei 442000,China;Anesthesia,Hubei Province Shiyan City Yunyang District Hospital of Traditional Chinese Medicine,Shiyan,Hubei 442000,China)

机构地区：[1]湖北医药学院附属太和医院麻醉科,湖北十堰442000 [2]湖北省十堰市郧阳区中医医院麻醉科,湖北十堰442500

出　　处：《中国优生与遗传杂志》2023年第3期453-459,共7页Chinese Journal of Birth Health & Heredity

基　　金：2021年度湖北省教育厅科学研究计划资助项目(Q20212104)。

摘　　要：目的基于高迁移率族蛋白B1(HMGB1)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)轴探究橙皮苷抑制轴对七氟醚(Sev)诱导的新生大鼠的神经保护作用。方法将SPF级SD新生大鼠72只,随机分为Control组、Sev组、Hsd-L组、Hsd-H组、Hsd-H+Nigericin组。Morris水迷宫实验检测大鼠认知能力;H-E观察海马组织形态;TUNEL法检测海马组织细胞凋亡率;ELISA测定IL-1β、S100β、BDNF、NGF水平;免疫组化法检测Cleaved-caspase-3、Bax、Bcl-2的表达;Westernblotting检测海马组织HMGB1、NLRP3、Cleaved-caspase-1蛋白的表达水平。结果与Control组相比,Sev组大鼠海马组织出现细胞排列紊乱、间隙增大、核固缩,逃避潜伏期、细胞凋亡率、IL-1β、S100β、Cleaved-caspase-3、Bax、HMGB1、NLRP3、Cleaved-caspase-1水平均升高,穿越平台次数、BDNF、NGF、Bcl-2水平降低(P<0.05)。与模型组相比,Hsd-L和Hsd-H组海马组织损伤减轻,逃避潜伏期、细胞凋亡率、IL-1β、S100β、Cleaved-caspase-3、Bax、HMGB1、NLRP3、Cleaved-caspase-1水平均降低,穿越平台次数、BDNF、NGF、Bcl-2水平升高(P<0.05)。NLRP3的激活剂Nigericin明显减弱了Hsd对Sev诱导的新生大鼠海马神经损伤的保护作用。结论橙皮苷可能通过抑制HMGB1/NLRP3轴实现对Sev诱导的新生大鼠的神经保护作用。Objective To explore the neuroprotective effect of hesperidin-inhibited axis on sevoflurane(Sev)-induced neonatal rats based on the high mobility group box protein B1(HMGB1)/NOD-like receptor pyrin domain-related protein 3(NLRP3)axis.Methods Seventy-two SPF SD newborn rats were randomly divided into Control group,Sev group,Hsd-L group,Hsd-H group and Hsd-H+Nigericin group.The Morris water maze test was used to detect the cognitive ability of rats.H-E was applied to observe hippocampal tissue morphology.TUNEL method was applied to detect the apoptosis rate of hippocampal tissue.ELISA was applied to measure levels of serum IL-1β,S100β,BDNF and NGF.Immunohistochemistry was applied to detect the expression of Cleaved-caspase-3,Bax,and Bcl-2.Western blotting was applied to detect the expression levels of HMGB1,NLRP3 and Cleaved-caspase-1 proteins in hippocampus.Results Compared with the Control group,the hippocampus of the Sev group showed disordered cell arrangement,enlarged gap,pyknosis and other pathological changes,the escape latency,apoptosis rate,the levels of IL-1β,S100β,Cleaved-caspase-3,Bax,HMGB1,NLRP3,and Cleaved-caspase-1elevated,the times of crossing the platform,the levels of BDNF,NGF,and Bcl-2 decreased(P<0.05).Compared with the model group,Hsd-L and Hsd-H groups had less damage to the hippocampus,the escape latency,apoptosis rate,the levels of IL-1β,S100β,Cleaved-caspase-3,Bax,HMGB1,NLRP3,and Cleaved-caspase-1 decreased,the times of crossing the platform,the levels of BDNF,NGF,and Bcl-2 elevated(P<0.05).The activator of NLRP3,Nigericin,greatly attenuated the protective effect of Hsd on Sev-induced hippocampal nerve injury in neonatal rats.Conclusion Hesperidin may achieve neuroprotective effect on Sev-induced neonatal rats by inhibiting the HMGB1/NLRP3 axis.

关 键 词：橙皮苷 HMGB1/NLRP3轴 七氟醚 新生大鼠 神经保护 

分 类 号：R285.5[医药卫生—中药学]