枸杞糖肽通过抑制铁死亡减轻高血糖大鼠脑缺血/再灌注损伤  

Lycium barbarum glycopeptide attenuates cerebral ischemia/reperfusion injury in hyperglycemic rats through inhibition of ferroptosis

作　　者：李鹏 杨晶[1] 马艳梅 张建忠 景丽 LI Peng;YANG Jing;MA Yan-mei;ZHANG Jian-zhong;JING Li(Dept of Pathology,School of Basic Medical Sciences,Ningxia Medical University,Yinchuan 750004,China;Radiology Dept of the General Hospital,Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学基础医学院病理学系,宁夏银川750004 [2]宁夏医科大学总医院放射科,宁夏银川750004

出　　处：《中国药理学通报》2023年第11期2043-2049,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 31960177);宁夏回族自治区自然科学基金资助项目(No 2023AAC03562)。

摘　　要：目的探讨枸杞糖肽(Lycium barbarum glycopeptide,LbGp)是否通过抑制铁死亡减轻高血糖大鼠脑缺血/再灌注损伤(cerebral ischemia/reperfusion injury,CIRI)。方法SD大鼠随机分为高血糖假手术组、高血糖短暂性大脑中动脉栓塞再灌注(tMCAO/R)组、高血糖LbGp预处理tMCAO/R组及高血糖去铁酮阳性对照tMCAO/R组。采用改良神经功能缺损评分(mNSS)法评价神经功能缺损情况;磁共振T2加权成像测量脑梗死体积;HE染色观察组织病理学变化;试剂盒检测脑组织铁含量、GSH/GSSG比值、SOD活性、T-AOC及MDA含量;免疫组织化学法或Western blot检测TFR1、DMT1、FPN1、ACSL4、GPX4蛋白的表达。结果与高血糖tMCAO/R组相比,LbGp组mNSS、脑梗死体积、核固缩神经元数量,以及脑组织铁含量、MDA含量、TFR1、DMT1、ACSL4蛋白表达量均降低,GSH/GSSG比值、SOD活性、T-AOC、FPN1及GPX4蛋白表达均增加。结论LbGp可减轻高血糖大鼠脑CIRI,其机制可能与抑制铁死亡的发生有关。Aim To investigate whether Lycium barbarum glycopeptide(LbGp)attenuates cerebral ischemia/reperfusion injury(CIRI)in hyperglycemic rats by inhibiting ferroptosis.Methods SD rats were randomly divided into hyperglycemic sham-operated group,hyperglycemic tMCAO/R group,hyperglycemic LbGp pretreated tMCAO/R group and hyperglycemic deferiprone positive control tMCAO/R group.Neurological deficits were evaluated by modified neurological severity score(mNSS);brain infarct volume was assessed by magnetic resonance T2-weighted imaging;histopathological changes were observed by HE staining;commercial kits were used to detect brain tissue iron content,GSH/GSSG ratio,SOD activity,total antioxidant capacity(T-AOC)and MDA content;immunohistochemistry or Western blot were used to detect transferrin receptor 1(TFR1),divalent metal transporter 1(DMT1),ferroportin 1(FPN1),acyl-CoA synthetase long-chain family member 4(ACSL4),and glutathione peroxidase 4(GPX4)protein expressions.Results Compared with the hyperglycemic tMCAO/R group,mNSS,cerebral infarct volume,number of pyknotic neurons,brain iron content,MDA content,TFR1,DMT1 and ACSL4 protein expressions decreased,and GSH/GSSG ratio,SOD activity,T-AOC,FPN1 and GPX4 protein expressions increased in the LbGp group.Conclusions LbGp attenuates CIRI in hyperglycemic rats,and its mechanism may be related to the inhibition of ferroptosis.

关 键 词：枸杞糖肽 高血糖 脑缺血/再灌注损伤 神经保护 铁死亡 GPX4 

分 类 号：R-332[医药卫生] R282.71R587.1R591.1R743.31