目的 研究田蓟苷联合有氧训练对阿尔茨海默病(AD)大鼠认知功能的影响.方法 将大鼠分为空白组、模型组、对照组、低剂量实验组、中剂量实验组、高剂量实验组和联合组,每组12只.空白组为进行假手术的大鼠,其他组用双侧海马注射β-淀粉样蛋白1-42(Aβ1-42)建立的AD模型大鼠.建模1周后,对照组和联合组大鼠进行跑台有氧训练,其他组大鼠安静饲养.空白组、模型组、对照组灌胃给予0.5％羧甲基纤维素钠(CMC)2 mL.低、中、高剂量组大鼠灌胃给予5、10和20 mg·kg-1·d-1田蓟苷2mL.联合组灌胃20 mg·kg-1·d-1的田蓟苷2mL.共给药6周.用Morris水迷宫实验评估认知功能,用定量逆转录聚合酶链反应法检测海马β-淀粉样前体蛋白裂解酶1(BACE1)mRNA的表达水平,用蛋白质印迹法检测海马核因子-κB(NF-κB)p65磷酸化的表达水平.结果 空白组、模型组、对照组、低剂量实验组、中剂量实验组、高剂量实验组和联合组的逃避潜伏期分别为(20.16±2.06)、(60.45±6.55)、(46.52±2.90)、(42.80±3.15)、(41.19±2.54)、(35.66±2.82)和(28.49±1.97)s,BACE1 mRNA 相对表达量分别为 1.00±0.06、7.88±0.49、6.02±0.38、4.96±0.57、3.01±0.21、1.98±0.17 和 1.48±0.11,磷酸化NF-κB p65(p-NF-κB p65)蛋白相对表达水平分别为0.11±0.03、1.46±0.11、0.89±0.10、0.71±0.06、0.37±0.05、0.29±0.02 和 0.15±0.01,模型组与空白组比较,低、中、高剂量实验组与模型组比较,联合组与高剂量实验组比较,在统计学上差异均有统计学意义(均P＜0.05).结论 田蓟苷联合有氧训练改善了 AD大鼠的认知功能,其机制可能与抑制NF-κB信号通路介导的炎症有关.
Objective To explore the effect of tilianin combined with aerobic training on cognitive function of rats with Alzheimer's disease(AD).Methods Rats were divided into 7 groups:blank group,model group,control group,low dose experimental group,medium dose experimental group,high dose experimental group and combination group,12 rats in each group.The rats in blank group were sham operated,and other groups were AD model rats established by bilateral hippocampal injection of amyloid-beta peptide 1-42(A(31-42).One week after modeling,the rats in control group and combination group were trained on the treadmill,and the rats in other groups were fed quietly.The rats in blank group,model group and control group were given 0.5％carboxymethyl cellulose sodium(CMC)2 mL.The rats in low,medium and high dose experimental groups were given intragastric administration of 5,10 and 20 mg·kg-1·d-1tilianin 2 mL.The rats in combined group were given 20 mg·kg-1·d-1 tilianin 2 mL by gavage.The drug was given for 6 weeks.Cognitive function was evaluated by Morris water maze test.The level of Beta-site APP cleaving enzyme protein 1(BACE1)mRNA in hippocampus was measured by quantitative reverse transcription polymerase chain reaction.The phosphorylation level of nuclear factor-κB(NF-κB)p65 in hippocampus was detected by Western blot.Results The escape latencies of blank group,model group,control group,low dose experimental group,medium dose experimental group,high dose experimental group and combination group were(20.16±2.06),(60.45±6.55),(46.52±2.90),(42.80±3.15),(41.19±2.54),(35.66±2.82)and(28.49±1.97)s;the relative expression of BACE1 mRNA were 1.00±0.06,7.88±0.49,6.02±0.38,4.96±0.57,3.01±0.21,1.98±0.17 and 1.48±0.11;the relative phosphorylation levels of NF-κB p65 were 0.11±0.03,1.46±0.11,0.89±0.10,0.71±0.06,0.37±0.05,0.29±0.02 and 0.15±0.01.Compared between model group and blank group,comparison between low,medium,high dose experimental group and model group,comparison between combination group and high dose experimental group all showed statistically significant differences(all P＜0.05).Conclusion Tilianin combined with aerobic training can improve the cognitive function of AD rats,and its mechanism may be related to the inhibition of inflammation mediated by NF-κB signal pathway.
黄波;吴卫东;王峥;朱敬生
郑州大学体育学院,河南郑州 450044郑州大学体育学院,河南郑州 450044||河北师范大学体育学院,河北石家庄 050024郑州大学体育学院,河南郑州 450044||上海体育学院运动科学学院,上海 200438
中医学
田蓟苷;有氧训练;阿尔茨海默病;认知功能;核因子-κB
tilianin;aerobic training;Alzheimer's disease;cognitive function;nuclear factor-κB
《中国临床药理学杂志》 2024 (011)
1618-1622 / 5
河南省科技厅科技发展基金资助项目(202102310324)
10.13699/j.cnki.1001-6821.2024.11.016
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