木犀草素对衰老模型大鼠记忆功能及凋亡相关蛋白的影响  

Effects of hesperetin on memory function and apoptosis-related protein expression in senile model rats

作　　者：李佳昕 郝金奇[1] 余杰 石郑阳 石继海 余艳琴[1,3] Li Jiaxin;Hao Jinqi;Yu Jie;Shi Zhengyang;Shi Jihai;Yu Yanqin(College of Public Health,Baotou Medical College,Baotou 014040,China;College of Nursing,Baotou Medical College,Baotou 014040,China;The First Affiliated Hospital of Baotou Medical College,Baotou 014010,China)

机构地区：[1]包头医学院公共卫生学院,包头014040 [2]包头医学院护理学院,包头014040 [3]包头医学院第一附属医院,包头014010

出　　处：《中华行为医学与脑科学杂志》2024年第3期233-239,共7页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：内蒙古自治区科技创新引导项目(CXYD2020BT08)。

摘　　要：目的探讨不同剂量的木犀草素对D-半乳糖致衰老大鼠记忆功能及凋亡蛋白的影响。方法SPF级雄性6~8周龄Wistar大鼠48只,按照随机数字表法分为对照组、模型组、木犀草素低剂量组(25 mg/kg)、中剂量组(50 mg/kg)、高剂量组(100 mg/kg)及维生素C组(100 mg/kg),每组8只。采用D-半乳糖(1000 mg/kg)皮下注射法制备大鼠衰老模型,同时使用木犀草素进行预防性灌胃治疗。Morris水迷宫实验评估小鼠学习记忆能力;透射电镜检测大鼠海马神经元形态;分光光度法检测检测大鼠大脑皮质中白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)、总抗氧化能力(total antioxidant capacity,T-AOC)水平;RT-PCR检测miR-34a mRNA表达;Western blot技术检测沉默调节蛋白1(sirtuin 1,SIRT1)、B淋巴细胞瘤2(B-cell lymphoma-2,Bcl-2)、裂解caspase-3、p53、p21的表达水平。采用SPSS 22.0进行统计分析,多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果(1)6组大鼠首次找到原平台时间差异有统计学意义(F=120.93,P<0.001),模型组大鼠首次找到原平台时间[(54.61±3.60)s]高于对照组[(10.54±4.27)s](P<0.05),木犀草素低、中、高剂量组大鼠首次找到原平台时间[(45.50±3.81)s,(37.46±2.94)s,(32.32±3.14)s]均低于模型组[(54.61±3.60)s](均P<0.05)。(2)6组大鼠大脑皮质中SOD、MDA、T-AOC、TNF-α、IL-1β和IL-6水平均差异具有统计学意义(F=281.636,75.119,208.228,38.999,28.428,52.767,均P<0.001)。模型组较对照组相比炎症因子和抗氧化指标异常,木犀草素中、高剂量组大鼠大脑皮质中SOD、T-AOC含量高于模型组(均P<0.05);MDA、TNF-α、IL-1β和IL-6水平低于模型组(均P<0.05)。(3)6组大鼠的miR-34a mRNA相对表达水平差异有统计学意义(F=81.439,P<0.001)。木犀草素不同剂量组大ObjectiveTo investigate the effect and mechanism of different doses of luteolin on memory function and apoptosis-related proteins of aging rats induced by D-galactose.MethodsForty-eight SPF-grade male Wistar rats aged 6-8 weeks were randomly divided into control group,model group,luteolin low-dose group(25 mg/kg),medium-dose group(50 mg/kg),high-dose group(100 mg/kg),and vitamin C group(100 mg/kg),with 8 rats in each group.D-galactose(1000 mg/kg)was subcutaneously injected to establish the aging rat model,while luteolin was used for preventive treatment.The Morris water maze test was used to evaluate the learning and memory abilities of the rats.Transmission electron microscopy was used to detect the morphology of hippocampal neurons in rats.Spectrophotometry was used to detect the levels of interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD),malondialdehyde(MDA),and the total antioxidant capacity(T-AOC).RT-PCR was used to detect miR-34a mRNA expression.Western blot technique was used to detect the expression levels of silent regulator protein 1(SIRT1),B-cell lymphoma-2(Bcl-2),cleaved caspase-3,p53,and p21.Statistical analysis was performed using SPSS 22.0,and one-way ANOVA was used for multi-group comparison,followed by LSD-t test for further pairwise comparisons.Results(1)The differences in escape latency among the 6 groups of rats were statistically significant(F=120.93,P<0.001).The latency of first finding the platform location of the model group rats((54.61±3.60)s)was higher than that of the control group((10.54±4.27)s)(P<0.05).The latency of first finding the platform location of rats in the low,medium and high dosage groups of luteolin((45.50±3.81)s,(37.46±2.94)s,(32.32±3.14)s)was lower than that of the model group((54.61±3.60)s)(all P<0.05).(2)The differences of SOD,MDA,T-AOC,TNF-α,IL-1β,and IL-6 levels in the cerebral cortex of the 6 groups of rats were all statistically significant(F=281.636,75.119,208.228,38.999,28.428,52.767,all P<0.001).Compa

关 键 词：木犀草素 衰老 记忆 海马 沉默信息调节因子1 P53蛋白 凋亡 

分 类 号：R285.5[医药卫生—中药学]