高铜负荷对大鼠神经行为和SIRT3/PGC-1α信号通路的影响OA
Influence of high copper load on neurobehavior and the sirtuin 3/peroxisome proliferator-activated receptor-γ co-activator-1α signaling pathway in rats
目的 探讨高铜负荷对大鼠神经行为的影响,并基于线粒体去乙酰化酶3(SIRT3)/过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)信号通路探讨其可能的作用机制.方法 将50只SD成年大鼠采用随机数字法分为模型(MG)组,空白(NG)组,每组25只.模型组予以含硫酸铜1 g/kg的高铜饲料及0.185%硫酸铜溶液(以去离子水配制)喂养制备高铜负荷大鼠模型,12周后采用穿梭箱试验和爬杆试验观察大鼠的神经行为变化情况,并采用蛋白质印迹法(WB)和免疫荧光染色法检测大鼠海马组织SIRT3、PGC-1α蛋白的表达水平.结果 穿梭箱试验中,模型组大鼠受刺激后主动回避反应次数较空白组明显减少(P<0.01),主动回避反应时间、被动回避反应时间明显增加(P<0.01);爬杆试验显示模型组大鼠的爬杆时间较空白组明显升高(P<0.01);蛋白质印迹法和免疫荧光染色法检测模型组大鼠较空白组大鼠海马组织中SIRT3/PGC-1α的蛋白表达水平均明显减少(P<0.05).结论 高铜负荷对大鼠神经行为有明显影响,调节海马神经元SIRT3/PGC-1α信号通路的表达是其可能的作用机制.
Objective To investigate the influence of high copper load on neurobehavior in rats and its possible mechanism of action based on the deacetylase sirtuin 3(SIRT3)/peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α)signaling pathway.Methods A total of 50 adult Sprague-Dawley rats were randomly divided into model group and blank group,with 25 rats in each group.The rats in the model group were fed with 1 g/kg high-copper diet and 0.185%copper sulfate solution(prepared using deionized water)to establish a rat model of high copper load,and after 12 weeks,the shuttle box test and the pole-climbing test were used to observe neurobehavioral changes,while Western blotting and immunofluorescent staining were used to measure the protein expression levels of SIRT3 and PGC-1α in hippo-campal tissue.Results The shuttle box test showed that compared with the blank group,the model group had a signifi-cant reduction in the number of times of active avoidance reaction after stimulation(P<0.01)and significant increases in the times of active avoidance reaction and passive avoidance reaction(P<0.01);the pole-climbing test showed that com-pared with the blank group,the model group had a significant increase in pole-climbing time(P<0.01).Western blotting and immunofluorescent staining showed that compared with the blank group,the model group had significant reductions in the protein expression levels of SIRT3 and PGC-1α in hippocampal tissue(P<0.05).Conclusion High copper load has a marked influence on the neurobehavior of rats,possibly by regulating the expression of the SIRT3/PGC-1α signal path-way in hippocampal neurons.
姜姗;金珊;方向;王洋洋;高婷
安徽中医药大学第一临床医学院,安徽 合肥 230038安徽中医药大学第一附属医院神经内科,安徽 合肥 230031||安徽中医药大学新安医学教育部重点实验室,安徽 合肥 230038安徽中医药大学第一附属医院神经内科,安徽 合肥 230031||安徽中医药大学新安医学教育部重点实验室,安徽 合肥 230038安徽中医药大学第一临床医学院,安徽 合肥 230038安徽中医药大学第一临床医学院,安徽 合肥 230038
医药卫生
肝豆状核变性大鼠神经行为SIRT3/PGC-1α信号通路
Hepatolenticular degenerationNeurobehavior in ratsSirtuin 3/peroxisome proliferator-activated receptor-γ coactivator-1αSignaling pathway
《中风与神经疾病杂志》 2026 (3)
254-258,5
安徽省自然科学基金面上项目(2008085MH264、2208085MH271)国家中医药管理局第六批全国老中医药专家学术经验继承项目(国中医药人教发[2017]年29号)
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