乙酰葛根素纳米制剂联合Wnt/β-catenin信号通路在大鼠脑缺血再灌注损伤模型中调节自噬发挥神经保护作用  

Acetyl puerarin nanoparticle formulations combined with Wnt/beta⁃catenin signaling pathway modulate autophagy to exert a neuroprotective effect in the rat model of cerebral ischemia/reperfusion injury

作　　者：杜立[1] 杨振兴[2] 孙倩[1] DU Li;YANG Zhenxing;SUN Qian(Dept.of Anesthesiology,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China;Dept.of Neurosurgery,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China)

机构地区：[1]武汉大学人民医院麻醉科,湖北武汉430060 [2]武汉大学人民医院神经外科,湖北武汉430060

出　　处：《武汉大学学报（医学版）》2024年第6期637-642,共6页Medical Journal of Wuhan University

基　　金：湖北省自然科学基金资助项目(编号:2022CFB680);武汉大学自主科研项目(编号:2042022kf1119)。

摘　　要：目的:探索乙酰葛根素纳米制剂——乙酰葛根素-聚乳酸-乙醇酸纳米颗粒(AP-PLGA-NPs)通过与Wnt/β-catenin通路的联合作用在大鼠脑缺血再灌注损伤(CIRI)期间对自噬的影响。方法:将48只雄性SpragueDawley(SD)大鼠随机分为3组(16只/组):实验组(AP-PLGA-NPs联合Wnt/β-catenin激动剂氯化锂)、CIRI组和对照组。制备AP-PLGA-NPs后,采用大脑中动脉缝合闭塞法,在缺血2 h后再灌注24 h,建立CIRI大鼠模型。然后使用Garcia神经功能评分评估所有组的神经行为表现。使用2%三苯基四氮唑(TTC)对脑梗死体积进行鉴定和染色,并通过Western Blot和密度测定法测定皮层β-catenin、Bcl-2和Bax的表达。结果:与CIRI组相比,实验组神经行为评分明显降低(P<0.05),脑梗死体积相应减小(P<0.05);与CIRI组相比,实验组β-catenin表达增加,皮质Bax和Bcl-2表达也明显降低(P<0.05)。结论:AP-PLGA-NPs联合Wnt/β-catenin信号可以下调自噬水平、减轻大鼠的脑缺血再灌注损伤。Objective:To explore the effect of acetyl puerarin nanoparticle formulations,acetyl puerarin poly⁃lactic acid glycolic acid nanoparticles(AP⁃PLGA⁃NPs),combined with the Wnt/β⁃catenin signal on the down⁃regulation of autophagy during cerebral ischemia/reperfusion injury(CIRI)in rats.Methods:A total of 48 male Sprague Dawley(SD)rats were randomly divided into three groups(16 rats/group):experimental group(AP⁃PLGA⁃NPs combined with Wnt/β⁃catenin agonist,lithium chloride),CIRI group,and control group.After preparation of AP⁃PLGA⁃NPs,the CIRI rat models were estab⁃lished by middle cerebral artery suture occlusion method and reperfusion for 24 hours after 2 hours of ischemia.Then the neurobehavioral performance of all groups was evaluated with Garcia Neurological Function Score.The volume of cerebral infarction was identified and stained with 2%triphenyltetra⁃zolium(TTC),and the expression ofβ⁃catenin,Bcl⁃2,and Bax in the cortex was measured by Western Blot and densitometry.Results:Compared with the CIRI group,the neurobehavioral score in the experimental group was significantly lower(P<0.05),and the volume of cerebral infarction was correspondingly reduced(P<0.05);while the expression ofβ⁃catenin in the experimental group increased,and the expression of Bax and Bcl⁃2 in cortex decreased significantly(P<0.05).Conclu⁃sion:AP⁃PLGA⁃NPs combined with Wnt/β⁃catenin signal can reduce autophagy level and alleviate ce⁃rebral ischemia/reperfusion injury in rats.

关 键 词：乙酰葛根素-聚乳酸-乙醇酸纳米颗粒 WNT/Β-CATENIN信号通路 自噬 脑缺血再灌注损伤 神经保护 

分 类 号：R743.33[医药卫生—神经病学与精神病学]