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

作　　者：陈国蕾 沈紫红 闫斯旸 刘畅[1] 梁露丹 吴新贵[1] CHEN Guolei;SHEN Zihong;YAN Siyang;LIU Chang;LIANG Ludan;WU Xin’gui(Department of Traditional Chinese Medicine,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学第一附属医院中医科,南宁530021

出　　处：《广西医科大学学报》2025年第2期218-225,共8页Journal of Guangxi Medical University

基　　金：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)。

摘　　要：目的:探讨甘草酸对脑缺血再灌注大鼠的保护作用,并通过高迁移率组蛋白B1(HMGB1)介导的细胞焦亡来阐述其作用机制。方法:将45只雄性SD大鼠随机分为假手术(sham)组、大脑中动脉闭塞/再灌注(MCAO/R)组和甘草酸组。MCAO/R组和甘草酸组采用Longa改良线栓法制备MCAO/R模型,甘草酸组灌胃给予20 mg/kg甘草酸溶液,连续7 d。采用改良神经功能受损评分(mNSS)评估大鼠神经功能缺损情况;2,3,5-氯化三苯基四氮唑染色(TTC)染色法检测大鼠脑梗死体积百分比;苏木精—伊红(HE)染色和尼式(Nissl)染色检测大鼠脑组织梗死区域神经元等细胞的病理学变化;酶联免疫吸附试验(ELISA)检测大鼠脑组织梗死区肿瘤坏死因子-α(TNF-α)、白细胞介素1β(IL-1β)水平;western blotting法检测大鼠脑组织梗死区HMGB1以及焦亡相关核苷酸结合寡聚化结构域样NOD受体蛋白3(NLRP3)、GSDMD、半胱天冬酶1(caspase-1)的蛋白表达。结果:与sham组比较,MCAO/R组大鼠mNSS评分显著升高(P<0.05),大鼠脑组织梗死区神经元形态受损、排列紊乱、结构被破坏,HMGB1、NLRP3、GSDMD、caspase-1蛋白表达量显著升高(P<0.05),TNF-α、IL-1β表达量显著升高(P<0.05);与MCAO/R组比较,甘草酸组大鼠mNSS评分显著降低(P<0.05),大鼠脑组织梗死区坏死神经元数量显著减少,神经纤维排列整齐,HMGB1、NLRP3、GSDMD、caspase-1蛋白表达量显著降低(P<0.05),TNF-α、IL-1β表达量显著降低(P<0.05)。结论:甘草酸能够显著改善大鼠脑缺血再灌注损伤,其机制可能与HMGB1介导的焦亡通路有关。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 modified 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 areas of rat brain tissue were detected by hematoxylin-eosin(HE)staining and Nissl staining;the levels of tumor necrosis 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 nucleotidebinding 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 infarcted 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 expression levels of TNF-αand IL-1βwere 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 o

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 

分 类 号：R285[医药卫生—中药学]