雷帕霉素对小鼠双侧颈动脉狭窄模型自噬机制的影响  

Effects of Rapamycin on Autophagy in a Mouse Model of Bilateral Carotid Artery Stenosis

作　　者：林茵 薛钢 汤恒勇 陈娇 LIN Yin;XUE Gang;TANG Heng-yong;CHEN Jiao(Department of Neurology,Fengcheng Hospital,Fengxian District,Shanghai 201411,China)

机构地区：[1]上海市奉贤区奉城医院神经科,上海201411

出　　处：《中国临床神经科学》2022年第6期620-627,共8页Chinese Journal of Clinical Neurosciences

摘　　要：目的探讨雷帕霉素对慢性脑血流低灌注小鼠自噬机制的影响。方法30只SPF级C57BL/6J雄性小鼠随机分为假手术组、构建双侧颈总动脉狭窄(BCAS)模型(模型组)、模型+治疗组(均n=10)。模型+治疗组小鼠予以雷帕霉素灌胃治疗。Morris水迷宫实验检测小鼠学习记忆情况;苏木精-伊红染色观察小鼠额叶皮质和海马组织的病理变化;TUNEL染色检测小鼠额叶皮质和海马组织神经元凋亡;Western blot检测额叶皮质和海马中凋亡蛋白Bcl-2、Bax和自噬相关蛋白LC3、P62、Aβ1-42、APP、BACE1蛋白的表达。结果与假手术组比较,模型组小鼠认知损害加重、额叶皮质和海马神经元损伤、氧化应激水平提高、神经元凋亡率升高,Bcl-2蛋白下降,Bax、LC3-Ⅱ、P62、Aβ1-42、APP和BACE1蛋白升高(均P<0.05);与模型组比较,模型+治疗组小鼠认知能力提高,额叶皮质和海马神经元损伤减轻,氧化应激水平下降,神经元凋亡率降低,Bcl-2蛋白、LC3-Ⅱ蛋白水平升高,Bax蛋白,P62、Aβ1-42、APP和BACE1蛋白水平降低(均P<0.05)。结论雷帕霉素通过激活自噬改善慢性脑血流低灌注小鼠认知损害。Aim To investigate the effect of rapamycin on autophagy in a mouse model of bilateral carotid artery stenosis.Methods Thirty SPF C57BL/6J male mice were randomly divided into a sham operation group,an operation group(BCAS),an operation+treatment group(BCAS+Rapa),10 in each group.The mice model of bilateral common carotid artery stenosis(BCAS)was established.Mice in BCAS+Rapa group were treated with rapamycin by gavage.Morris water maze test was used to test the learning and memory of mice.The pathological changes of frontal cortex and hippocampus were observed by HE staining.TUNEL staining was used to detect neuronal apoptosis in the frontal cortex and hippocampus of mice.Western blotting was used to detect the changes of apoptotic protein Bcl-2,Bax and autophagy related protein LC3,P62 in the frontal cortex and hippocampus,and the expression of Aβ1-42,APP,BACE1 protein.Results Compared with the sham group,the cognitive impairment,neuron damage in frontal cortex and hippocampus,oxidative stress level and neuronal apoptosis rate were increased,Bcl-2 protein was decreased and Bax,LC3-Ⅱ,P62,Aβ1-42,APP and BACE1 protein were increased in the BCAS group(all P<0.05).Compared with the BCAS group,the cognitive ability of the mice in the BCAS+Rapa group was increased,the damage of neurons in the frontal cortex and hippocampal neurons was reduced,the oxidative stress level was decreased,the neuronal apoptosis rate was decreased,the level of Bcl-2 protein was increased,and the level of Bax was decreased,the LC3-Ⅱprotein level was increased,the P62 level was decreased,and the Aβ1-42,APP,BACE1 protein levels were decreased(all P<0.05).Conclusion Rapamycin ameliorates cognitive dysfunction by activating autophagy in mice with chronic cerebral hypoperfusion.

关 键 词：雷帕霉素 认知损害 自噬 慢性脑血流低灌注 模型 

分 类 号：R743[医药卫生—神经病学与精神病学]