摘要
目的探讨足细胞骨架结构蛋白α-actinin-4与多柔比星肾病大鼠机体氧化应激状态的关系,并从分子水平推测贝那普利降低尿蛋白的作用机制。方法实验组Wistar大鼠经尾静脉一次性注射多柔比星5mg/kg建立动物模型,术后药物干预组予贝那普利6mg/(kg.d)灌胃,对照组则行等量9g/L盐水灌胃,观察2组大鼠尿蛋白、氧化应激指标丙二醛(MDA)、超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)变化。链酶抗生物素蛋白-生物素过氧化酶复合物(SABC)免疫组织化学染色,观察α-actinin-4在其肾小球中的分布及表达改变。结果实验组多柔比星注射后7d即有T-AOC活性递减,α-actinin-4蛋白阳性表达递增,且α-actinin-4由均匀点线样分布,逐渐向不连续粗颗粒状、连续较粗线样、斑片样的分布模式转变;在14～28d,实验组24h尿蛋白量、MDA渐增,SOD递减,与对照组比较均有显著性差异(Pa<0.05)。与实验组比较,28～35d贝那普利干预组24h尿蛋白量及MDA显著降低,SOD、T-AOC活性明显增强;免疫组织化学染色示α-actinin-4表达减弱,并呈线样分布,且紊乱程度减轻(Pa<0.05)。相关性分析示α-actinin-4与24h尿蛋白量、MDA均呈正相关(r=0.948,0.825Pa=0),与SOD、T-AOC均呈负相关(r=-0.956,-0.873Pa=0)。结论多柔比星肾病大鼠α-actinin-4分布及表达的改变与蛋白尿的发生及机体氧化应激状态存在相关性。贝那普利降尿蛋白的作用可能与改善机体氧化应激,影响α-actinin-4分布或表达有关。
ObjectiveTo explore the relationship between α-actinin-4 and oxidative stress in rats with Doxorubicin nephropathy,and to conjecture the mechanism of Benazepril reducing urine protein.MethodsThe model was established by a single intravenous injection of Doxorubicin（5 mg/kg）.Benazepril[6 mg/（kg·d）] was orally administered to medicine-treated group.Normal control group received the same volume of 9 g/L sodium chloride solution.Maleic dialdehyde（MDA）,superoxide dismutase（SOD）,total antioxygen capability（T-AOC） were detected by kit.Sterptavidin biotin peroxidase complex（SABC） immunohistochemistry were used to observe the expression and distribution of α-actinin-4 in rat glomeruli.ResultsSeven days after injection of Doxorubicin,the decrement of the activity of T-AOC,the progressive increase of expression of α-actinin-4 whose distribution was in derangement in experimental group.During 14 to 28 days,compared with normal control group,the urine protein,MDA increased significantly,while SOD decreased in experimental group（Pa〈0.05）.Benazepril-treated group showed significant reduction of urine protein and MDA,while the activity of SOD,T-AOC increased in comparison with experimental group during 28 to 35 days（Pa〈0.05）.The intensity of α-actinin-4 decreased while SABC immunohistochemistry showed a linear distribution.There was positive correlation between α-actinin-4 and urine protein,MDA（r=0.948,0.825Pa=0）,negative correlation between α-actinin-4 and SOD,T-AOC（r=-0.956,-0.873Pa=0）.ConclusionsThe expression of α-actinin-4 is associated with oxidative stress in rats with Doxorubicin nephropathy.The reducing effect of Benazepril is possibly achieved by stabilizing the expression and distribution of α-actinin-4.
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2009年第5期358-360,共3页
Journal of Applied Clinical Pediatrics
基金
安徽省自然科学基金项目资助(050430709)
