广西医科大学学报2025，Vol.42Issue(2)：218-225,8.DOI:10.16190/j.cnki.45-1211/r.2025.02.008
甘草酸通过抑制HMGB1介导的焦亡来减轻大鼠脑缺血再灌注损伤
Glycyrrhizic acid attenuates cerebral ischemia-reperfusion injury in rats by inhibiting HMGB1-mediated pyroptosis
摘要
Abstract
Objective:To explore the protective impact of glycyrrhizic acid on rats experiencing cerebral ischemia-reperfusion,and to elaborate its mechanism of action via high mobility group box-1 protein(HMGB1)-mediated pyroptosis.Methods:Forty five male Sprague-Dawley(SD)rats were randomly assigned to three groups:a sham-operated group(sham group),a middle cerebral artery occlusion/reperfusion group(MCAO/R group),and a glycyrrhizic acid group.The MCAO/R group and glycyrrhizic acid group had the MCAO/R model established using Longa's modified wire bolus method,and the glycyrrhizic acid group was administered 20 mg/kg glycyrrhizic acid solution by gavage for 7 d.The neurological deficits in rats were evaluated using the modi-fied neurological severity score(mNSS);the percentage of cerebral infarct volume in rats was detected by 2,3,5-triphenyltetrazolium chloride(TTC)staining;the pathologic changes in neurons and other cells in the infarcted ar-eas of rat brain tissue were detected by hematoxylin-eosin(HE)staining and Nissl staining;the levels of tumor ne-crosis factor-α(TNF-α)and interleukin-1β(IL-1β)in the infarcted areas of rat brain tissue were detected by enzyme-linked immunosorbent assay(ELISA);the protein expression of HMGB1,pyroptosis-related nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),GSDMD,and caspase-1 in the infarcted area of rat brain tissue was detected by western blotting.Results:Rats in the MCAO/R group exhibited significantly higher mNSS scores compared with those in the sham group(P＜0.05).The morphology of neurons in the in-farcted area of rat brain tissue was impaired,disorganized and structurally disrupted.Moreover,the expression levels of HMGB1,NLRP3,GSDMD,and caspase-1 proteins were significantly elevated(P＜0.05),and the ex-pression levels of TNF-α and IL-1β were also significantly increased(P＜0.05).Compared with the MCAO/R group,the mNSS scores of rats in the glycyrrhizic acid group were significantly decreased(P＜0.05),the number of necrotic neurons in the infarcted area of rat brain tissue was significantly reduced and the nerve fibers were ar-ranged orderly.Additionally,the expression levels of HMGB1,NLRP3,GSDMD,caspase-1 proteins,as well as TNF-α and IL-1β were significantly decreased(P＜0.05).Conclusion:Glycyrrhizic acid can significantly ame-liorate cerebral ischemia-reperfusion-injury in rats,and its mechanism may be related to the HMGB1-mediated pyroptosis pathway.关键词
脑缺血再灌注损伤/高迁移率组蛋白B1/焦亡/核苷酸结合寡聚化结构域样NOD受体蛋白3/炎症因子Key words
cerebral ischemia-reperfusion injury/high mobility group box-1 protein/pyroptosis/nucleotide-binding oligomerization domain-like receptor protein 3/inflammatory factor分类
医药卫生引用本文复制引用
陈国蕾,沈紫红,闫斯旸,刘畅,梁露丹,吴新贵..甘草酸通过抑制HMGB1介导的焦亡来减轻大鼠脑缺血再灌注损伤[J].广西医科大学学报,2025,42(2):218-225,8.基金项目
国家自然科学基金资助项目(No.81760885 （）
No.81360564) （）
广西自然科学基金重点项目(No.2017GXNSFDA198011) （No.2017GXNSFDA198011）
