褪黑素改善D-半乳糖诱导的小鼠认知功能障碍  

Effect of Melatonin on Cognitive Function of D-galactose-induced Aging Mouse Model

作　　者：张一丹 李婷婷[1] 许继取[2] 王婷[1,3] 王梓平 邓乾春 黄凤洪[2] 荣爽[1] Zhang Yidan;Li Tingting;Xu Jiqu(Academy of Nutrition and Health,Hubei Province Key Laboratory of Occupational Hazard Identification and Control,School of Public Health,Wuhan University of Science and Technology,Wuhan 430065,China;Oil Crops Research Institute,Chinese Academy of Agricultural Sciences,Wuhan 430062,China)

机构地区：[1]武汉科技大学营养与健康研究院,武汉430065 [2]中国农业科学院油料作物研究所,武汉430062 [3]武汉科技大学医学院药学系制药工艺研究所,武汉430065

出　　处：《华中科技大学学报（医学版）》2024年第5期586-590,628,共6页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.U21A20274);湖北省青年拔尖人才培养计划;现代农业产业技术体系资助(No.CARS-14-1-31)。

摘　　要：目的探讨褪黑素对D-半乳糖诱导的小鼠认知功能障碍的改善作用及潜在机制。方法将8周龄雄性C57BL/6小鼠随机分为3组:对照组(Control组)、D-半乳糖组(D-gal组)和D-半乳糖+褪黑素组(D-gal+MLT组),D-半乳糖采取腹腔注射(100 mg/kg),褪黑素采取灌胃(10 mg/kg),1次/d,持续3个月。采取Morris水迷宫实验评价小鼠认知功能;场电位长时程增强(long-term potentiation,LTP)实验评估药物对小鼠突触可塑性的影响;采用Western blots法测定小鼠海马和皮层组织中突触后致密蛋白(postsynaptic density-95,PSD95)、突触生长蛋白(synaptophysin,SYN)、沉默信息调节因子(sirtuin 1,SIRT1)及脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的蛋白表达水平。结果与对照组相比,D-gal组小鼠水迷宫实验逃避潜伏期延长,目标象限停留时间明显减少(均P<0.05),LTP受损(P<0.01),海马和皮层组织中PSD95、SYN、BDNF的蛋白表达显著降低(均P<0.05)。与D-gal组比较,褪黑素干预后(D-gal+MLT组)小鼠水迷宫实验逃避潜伏期显著缩短(P<0.05),LTP受损明显改善(P<0.01),海马和皮层组织中PSD95、SYN、SIRT1及BDNF蛋白表达水平显著增加(均P<0.05)。结论褪黑素对D-半乳糖诱导小鼠的认知功能障碍具有改善作用,其作用机制可能是通过提高SIRT1-BDNF表达水平,进而提高小鼠海马CA1区LTP,改善小鼠突触可塑性。Objective To investigate the effects of melatonin on the cognitive dysfunction induced by D-galactose in mice and the underlying mechanisms involved.Methods Eight-week-old male C57BL/6 mice were randomly divided into three groups:the control group,D-galactose group and D-galactose+melatonin group.D-galactose was administered by intraperitoneal injection(100 mg/kg),and melatonin was administered by gavage(10 mg/kg)once a day for three months.The Morris water maze was used to assess cognitive function.The effect of melatonin on synaptic plasticity was observed by long-term potentiation(LTP).The expression levels of PSD95,SYN,SIRT1 and BDNF in the hippocampus and cortex of the mice were determined by Western blotting.Results Compared with the control group,the D-gal group presented a longer escape latency,significantly shorter target quadrant dwell time(P<0.05),impaired LTP(P<0.01),and significantly lower PSD95,Synaptophysin and BDNF protein levels in the hippocampus and cortical tissues(P<0.05).The escape latency of the mice in the D-gal+MLT group significantly decreased(P<0.05),and LTP induction significantly improved(P<0.01).PSD95,Synaptophysin,SIRT1 and BDNF protein levels in the hippocampus and cortex were significantly increased in the D-gal+MLT group(P<0.05).Conclusion Melatonin can significantly improve the cognitive function of mice treated with D-galactose via a mechanism related to increasing the expression level of SIRT1-BDNF and improving the synaptic plasticity of mice,as shown by increased LTP in the hippocampal CA1 region.

关 键 词：褪黑素 D-半乳糖 认知障碍 长时程增强 SIRT1 

分 类 号：R749.16[医药卫生—神经病学与精神病学]