摘要
目的观察褪黑素能否通过MAPK/ERK信号通路,发挥对阿尔茨海默病大鼠小脑的神经保护作用。方法将32只♂SD大鼠随机分为4组:对照组、Aβ_(1-42)侧脑室注射组(AD)、褪黑素腹腔注射组(MT)、Aβ_(1-42)侧脑室注射结合褪黑素腹腔注射组(AD+MT)。HE染色观察各组大鼠小脑皮层的病理学变化;免疫荧光染色观察各组颗粒细胞标记物NeuN、浦肯野细胞标记物Calbindle和p-ERK蛋白的表达情况;Western blot检测各组小脑组织中p-ERK蛋白的表达。结果 HE染色结果显示,AD组大鼠小脑皮层的神经元数量减少,细胞排列紊乱,细胞形态改变,褪黑素可明显减轻侧脑室注射Aβ_(1-42)对小脑的病理学损害;免疫荧光结果显示,与AD组相比,AD+MT组颗粒细胞标记物NeuN的蛋白表达增加,以Calbindin标记的浦肯野细胞个数明显增多(P<0.01), p-ERK蛋白表达减少(P<0.01);Western blot结果显示,与AD组相比,AD+MT组小脑组织中p-ERK蛋白表达水平降低。结论褪黑素可能通过抑制MAPK/ERK信号通路的激活,发挥对小脑皮层神经原的保护作用。
Aim To investigate the effect of melatonin on neuroprotection in cerebellums of rats with Alzheimer′s disease via MAPK/ERK signaling pathway.Methods Thirty-two male Sprague-Dawley rats were randomly divided into four groups:control group,Aβ1-42 lateral ventricle injection group(AD),and melatonin intraperitoneal injection group(MT),and Aβ1-42 lateral ventricle injection combined with melatonin intraperitoneal injection group(AD+MT).The pathological changes of rat cerebellar cortex were detected by HE staining;the expression of NeuN(neuronal marker),Calbindin(Purkinje cell marker)and p-ERK protein in each group was detected by immunofluorescence;the expression of ERK and p-ERK in each group was determined by Western blot.Results The HE staining showed that the expression of neurons decreased,followed with the disordered arrangement and morphological alteration of cells in AD.Melatonin could significantly alleviate the pathological damage in cerebellum.Immunofluorescence results showed that compared with AD group,the expression of NeuN(neuronal marker)increased,the number of Purkinje cells marked by Calbindin significantly was up-regulated(P<0.01),and the expression of p-ERK was down-regulated in AD+MT group.Western blot showed that the expression of p-ERK was down-regulated by melatonin.Conclusions Melatonin may exert the neuroprotective effect and relieve the pathological changes by inhibiting the activation of MAPK/ERK signaling pathway.
作者
刘亭
毕竟
王盼
任丽莉
张露允
隋汝波
LIU Ting;BI Jing;WANG Pan;REN Li-li;ZHANG Lu-yun;SUI Ru-bo(The First Affiliated Hospital,Jinzhou Medical University,Jinzhou Liaoning121000,China;Key Lab of Neurodegenerative Diseases of Liaoning Province,Jinzhou Medical University,Jinzhou Liaoning121000,China;Dept of Neurobiology,Basic Medical College,Jinzhou Medical University,Jinzhou Liaoning121000,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2019年第3期402-407,共6页
Chinese Pharmacological Bulletin