基于TLR4/MyD88/NF-κB通路探讨早期跑步运动对血管性痴呆大鼠认知功能障碍的影响OA
Effects of early running exercise on cognitive dysfunction in rats with vas-cular dementia via TLR4/MyD88/NF-κB pathway
目的:基于TLR4/MyD88/NF-κB通路探讨早期跑步运动对血管性痴呆(VD)大鼠认知功能障碍的影响.方法:24只雄性SD大鼠随机分为假手术(Sham)组、VD组和跑步+VD组,每组8只.采用双侧颈总动脉闭塞方法构建VD模型.Sham组不结扎双侧颈总动脉,其余操作与VD组相同.建模后7 d,跑步+VD组大鼠进行跑步运动(15 m/min,30 min/d),持续4周.采用水迷宫实验评估各组大鼠空间记忆能力;尼氏染色检测海马死亡神经元数;比色法检测血清和海马组织中铁离子水平;ELISA法检测海马组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、IL-β、TNF-α和IL-6水平;Western blot法检测海马组织中P53、溶质载体家族7成员11(SLC7A11)、转铁蛋白受体1(TFR1)、谷胱甘肽过氧化酶-4(GPX4)、TLR4、MyD88和NF-κB蛋白表达.结果:与Sham组相比,VD组大鼠目标象限停留时间和穿越平台次数减少;海马死亡神经元数增加;血清铁离子水平升高;海马组织中铁离子、MDA、IL-β、TNF-α和IL-6水平增加,SOD和GSH水平降低;海马组织中P53、TFR1、TLR4、MYD88和NF-κB蛋白表达增加,SLC7A11和GPX4蛋白表达降低(P＜0.05).与VD组相比,跑步+VD组上述指标变化趋势均相反(P＜0.05).结论:早期跑步运动可能通过TLR4/MyD88/NF-κB通路抑制海马组织中铁死亡和炎症反应,从而改善VD大鼠认知功能障碍.
Aim:To explore the effects of early running exercise on cognitive dysfunction in rats with vascular dementia(VD)via TLR4/MyD88/NF-κB pathway.Methods:A total of 24 male SD rats were randomly divided into sham operation group(Sham group),VD group,and running+VD group,with 8 rats in each group.VD model was established using bilater-al common carotid artery occlusion method.The Sham group did not ligate the bilateral common carotid arteries,and the oth-er procedures were similar to those of the VD group.Seven days later,rats in the running+VD group were subjected to run-ning exercise(15 m/min,30 min/d)for 4 weeks.Then,water maze was used to evaluate the spatial memory ability.Nissl staining was used to detected the number of dead neurons in the hippocampus.The iron ion levels in serum and hippocampal tissue were measured using colorimetric method.ELISA method was used to detect the levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),IL-β,TNF-α,and IL-6 in hippocampal tissue.Western blot was used to detect the expression of P53,solute carrier family 7 member-11(SLC7A11),transferrin receptor 1(TFR1),glutathione per-oxidase 4(GPX4),TLR4,MyD88,and NF-κB proteins in the hippocampal tissue.Results:Compared with the Sham group,in the VD group,the target quadrant dwell time and platform crossing frequency decreased;the number of dead neurons in the hippocampus increased;the serum iron ion level increased;the levels of iron ions,MDA,IL-β,TNF-α,and IL-6 in-creased,while the levels of SOD and GSH decreased in hippocampal tissue;the expression of levels P53,TFR1,TLR4,MYD88,and NF-κB proteins increased,while the expression levels of SLC7A11 and GPX4 proteins decreased in hippocam-pal tissue(P＜0.05).Compared with the VD group,the trend of changes of the above indicators in the running+VD group was opposite(P＜0.05).Conclusion:Early running exercise may inhibit ferroptosis and inflammatory response in hipp-ocampal tissue through TLR4/MyD88/NF-κB pathway,thereby improving cognitive dysfunction in VD rats.
彭志锋;张继红;李晨旭
山西大同大学医学院生理学教研室 山西大同 037009山西大同大学医学院生理学教研室 山西大同 037009山西大同大学医学院生理学教研室 山西大同 037009
医药卫生
跑步血管性痴呆TLR4/MyD88/NF-κB通路认知功能障碍大鼠
runningvascular dementiaTLR4/MyD88/NF-κB pathwaycognitive dysfunctionrat
《郑州大学学报（医学版）》 2026 (5)
37-41,5
山西省基础研究计划项目(202303021211326)
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