摘要
目的探究吸入胰岛素对散发性阿尔茨海默病(sporadic Alzheimer’s disease,sAD)小鼠认知功能的影响及机制。方法采用链脲佐菌素(streptozotocin,STZ)侧脑室注射法构建散发性AD模型。C57BL/6 J小鼠随机分成3组:对照组(Con)、模型组(STZ-NS)和治疗组(STZ-INS),每组12只。治疗组经鼻吸入胰岛素0.87 U·d-1,对照组和模型组吸入同体积生理盐水。4周后行水迷宫实验检测小鼠的认知功能;免疫荧光实验检测小鼠海马区Iba1表达;Western blot检测各组小鼠海马GFAP、CD11b及NLRP3炎症小体通路相关蛋白的表达。另以脂多糖(lipopolysaccharide,LPS)刺激BV2细胞诱导其活化,不同浓度胰岛素预处理,Western blot检测NLRP3炎症小体通路相关蛋白的表达。结果与对照组小鼠相比,模型组小鼠的学习和记忆能力明显下降,海马区Iba1阳性细胞数量明显增加,GFAP、CD11b和NLRP3炎症小体通路相关蛋白的表达明显升高;吸入胰岛素后,小鼠的学习和记忆功能明显改善,海马区Iba1数量明显减少,GFAP、CD11b、NLRP3炎症小体通路相关蛋白的表达明显降低;细胞实验显示,胰岛素预处理可明显降低BV2细胞NLRP3炎症小体通路相关蛋白的表达。结论胰岛素能够减轻NLRP3炎症小体介导的神经炎症从而发挥神经保护作用,改善散发性AD小鼠的认知功能。
Aim To investigate the effect of inhaled insulin on cognitive function in sporadic AD mice and its mechanism.Methods The sporadic AD model was established by intracerebroventricular injection of streptozotocin.C57BL/6 J mice were randomly divided into three groups:control group(Con),model group(STZ-NS)and treatment group(STZ-INS),with 12 mice in each group.The treatment group received nasal inhalation of insulin 0.87 U·d-1,while the control group and model group received the same volume of saline.Morris water maze test was used to evaluate the cognitive function of each group after four weeks.Immunofluorescence staining was used to detect the expression of Iba1 in hippocampus of mice.The expressions of GFAP,CD11b and NLRP3 inflammasome pathway related proteins in hippocampus of mice were detected by Western blot.In addition,the BV2 cells were stimulated with lipopolysaccharide(LPS)to induce their activation,and were pretreated with different concentrations of insulin.The expressions of NLRP3 inflammasome pathway related proteins were detected by Western blot.Results Compared with the control group,the learning and memory function of the model group was impaired significantly,the number of Iba1 positive cells,the expression of GFAP,CD11b and NLRP3 inflammasome pathway related proteins in hippocampus significantly increased;intranasal insulin could significantly improve the learning and memory function of mice,decrease the number of Iba-1 positive cells and the expression of GFAP,CD11b and NLRP3 inflammasome pathway related proteins in hippocampus;cell experiments showed that insulin pretreatment could significantly reduce the expression of NLRP3 inflammasome pathway related proteins in BV2 cells.Conclusions Insulin can alleviate NLRP3 inflammasome-mediated neuroinflammation and improve cognitive function,which plays a neuroprotective role in sporadic AD mice.
作者
陶舒琪
范雯媛
郑昊宁
王通
陈燕春
周进
丁小娣
周风华
郭章玉
TAO Shu-qi;FAN Wen-yuan;ZHENG Hao-ning;WANG Tong;CHEN Yan-chun;ZHOU Jin;DING Xiao-di;ZHOU Feng-hua;GUO Zhang-yu(Dept of Clinical Pathology,School of Basic Medicine,Weifang Medical University,Weifang 261053,China;Neurologic Disorders and Regenerative Repair Key Laboratory of Shandong Province,Weifang 261053,China;Dept of Neurosurgery,Weifang People's Hospital,Weifang 261000,China;Dept of Histology and Embryology,School of Basic Medicine,Weifang 261053,China;Dept of Pharmacy,Weifang Medical University,Weifang 261053,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2023年第11期2050-2055,共6页
Chinese Pharmacological Bulletin
基金
山东省自然科学基金资助项目(No ZR2019BH060,ZR2020MH149)
山东省高等学校青创科技支持计划(No 2019KJK004)
潍坊市科技发展计划项目(No 2021YX063)。
