脑络通颗粒对脑缺血再灌注损伤大鼠的自噬及铜死亡相关蛋白的影响  

Effect of Naoluotong Granules on Autophagy and Cuproptosis Related Proteins in Rats with Cerebral Ischemia Reperfusion Injury

作　　者：马莉[1] 吴云虎[2] 梅灯 钱建华 赵俊杰 王鹏 李良勇[2] MA Li;WU Yunhu;MEI Deng;QIAN Jianhua;ZHAO Junjie;WANG Peng;LI Liangyong(Clinical College of Integrated Traditional Chinese and Western Medicine,Anhui University of Chinese Medicine,Hefei 230001,China;Department of Neurology,the First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031,China)

机构地区：[1]安徽中医药大学中西医结合学院,安徽合肥230001 [2]安徽中医药大学第一附属医院,安徽合肥230031

出　　处：《陕西中医药大学学报》2025年第2期95-101,共7页Journal of Shaanxi University of Chinese Medicine

基　　金：安徽省高等学校自然科学基金(2023AH050828,2024AH050955);安徽中医药大学人才支持计划项目(2023rcyb024)。

摘　　要：目的探讨脑络通颗粒对脑缺血再灌注损伤大鼠的自噬及铜死亡相关蛋白的影响。方法将SD大鼠随机分为假手术组(Sham组)、模型组(MCAO/R组)、脑络通颗粒组(NLT组)。MCAO/R组和脑络通颗粒组大鼠建立脑缺血再灌注损伤大鼠模型。造模后,药物干预组以20.2 g·kg-1(脑络通颗粒)灌胃相应药物进行处理,1次/d,连续7 d。Zea Longa法神经功能缺损程度评分,TTC染色观察脑梗死体积,比色法测定线粒体肿胀程度和线粒体ATP含量,TUNEL染色检测细胞凋亡,Western blot法检测线粒体自噬相关蛋白LC3Ⅱ/Ⅰ、P62、Beclin-1及铜死亡相关蛋白FDX1、LIAS、SLC31A1的表达。结果与Sham组相比,MCAO/R组大鼠神经功能缺损评分、脑梗死体积及神经元细胞凋亡率明显增加(P<0.05),脑组织线粒体出现明显的肿胀,线粒体ATP含量显著降低,线粒体自噬相关蛋白LC3Ⅱ/Ⅰ、Beclin-1、P62及铜死亡相关蛋白FDX1、LIAS、SLC31A1表达水平明显增加(P<0.05);与MCAO/R组相比,NLT组大鼠神经功能缺损评分、脑梗死体积及神经元细胞凋亡率明显降低,脑组织线粒体肿胀度明显减轻,线粒体ATP含量明显增加,线粒体自噬相关蛋白LC3Ⅱ/Ⅰ、Beclin-1表达水平明显上调,P62蛋白及铜死亡相关蛋白FDX1、LIAS、SLC31A1表达水平明显降低(P<0.05)。结论脑络通颗粒可能是通过下调铜死亡相关蛋白,进而增强脑缺血再灌注损伤大鼠线粒体自噬的活化,维持线粒体结构和功能的稳定,发挥对脑缺血再灌注损伤的保护作用。Objective To investigate the effect of Naoluotong granules on autophagy and cuproptosis related proteins in rats with cerebral ischemia reperfusion injury(CIRI).Methods SD rats were randomly divided into Sham group,Model group,and Naoluotong granule group.The middle cerebral artery occlusion and reperfusion(MCAO/R)animal model was established in the model group and the Naoluotong granule group rats.Naoluotong granule group was treated with Naoluotong granules(20.2 g·k g-1)by gavage once a day for 7 consecutive days after modeling.The Zea Longa method was used to evaluate the degree of neurological impairment,TTC staining for the volume of cerebral infarction,colorimetric method for the degree of mitochondrial swelling and mitochondrial ATP content,TUNEL staining for apoptosis,and Western blot for the expression of mitophagy related proteins LC3Ⅱ/Ⅰ,P62,Beclin-1,and cuproptosis related proteins FDX1,LIAS,SLC31A1.Results Compared with the Sham group,the Model group showed a significant increase in neurological deficit score,cerebral infarction volume,and neuronal apoptosis rate(P<0.05),a significant swelling of the brain tissue mitochondria,a significant decrease in the mitochondrial ATP content and a significant increase in the expression levels of mitophagy related proteins LC3Ⅱ/Ⅰ,Beclin-1 and P62,and cuproptosis related proteins FDX1,LIAS,and SLC31A1(P<0.05);Compared with the model group,the Naoluotong granule group showed a significant decrease in neurological deficit score,cerebral infarction volume,and neuronal apoptosis rate(P<0.05),a significant reduced swelling of the brain tissue mitochondria,a significant increase in the mitochondrial ATP content and the expression levels of mitophagy related proteins LC3Ⅱ/Ⅰand Beclin-1,and a significant decrease in the expression levels of P62 protein and cuproptosis related proteins FDX1,LIAS,and SLC31A1(P<0.05).Conclusion Naoluotong granules may downregulate cuproptosis related proteins,thereby enhancing the activation of mitophagy in CIRI rats,maintaining

关 键 词：脑络通颗粒 脑缺血再灌注损伤 线粒体自噬 铜死亡 

分 类 号：R332[医药卫生—人体生理学]