GluR2在慢性神经炎症致小鼠认知功能障碍中的作用  

Role of GluR2 in chronic neuroinflammation-induced cognitive dysfunction in mice

作　　者：何雪 杨唯奕 He Xue;Yang Weiyi(Department of Anesthesiology,Huaian First People′s Hospital,the Affiliated Hospital of Nanjing Medical University,Huaian 223300,China)

机构地区：[1]南京医科大学附属淮安市第一人民医院麻醉科,淮安223300

出　　处：《中华麻醉学杂志》2022年第3期269-273,共5页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(82002082)。

摘　　要：目的评价谷氨酸受体2(GluR2)在慢性神经炎症致小鼠认知功能障碍中的作用。方法成年雄性C57BL/6小鼠60只,8~10周龄,体重18~25 g,采用随机数字表法分为4组(n=15):对照+DMSO(二甲基亚砜)组(C+DMSO组)、对照+AMPA受体选择性非竞争性拮抗剂CFM-2组(C+CFM-2组)、LPS+DMSO组和LPS+CFM-2组。C+DMSO组和C+CFM-2组连续10 d每天腹腔注射生理盐水0.2 ml;第10天注射生理盐水后分别腹腔注射10%DMSO 0.165 ml或CFM-233μmol/kg(用10%DMSO稀释至0.165 ml)。LPS+DMSO组和LPS+CFM-2组连续10 d每天腹腔注射LPS 0.5 mg/kg(用生理盐水稀释至0.2 ml);第10天注射LPS后分别腹腔注射10%DMSO 0.165 ml或CFM-233μmol/kg(用10%DMSO稀释至0.165 ml)。给药结束后48 h时行Y迷宫实验,然后处死小鼠,取海马组织,采用Western blot法测定海马GluR2、离子化钙结合适配分子1(Iba1)和TNF-α的表达水平,免疫荧光法计数海马CA1区小胶质细胞。结果与C+DMSO组比较,LPS+DMSO组自发交替百分比降低,海马GluR2、Iba1和TNF-α表达上调,海马CA1区小胶质细胞数量增多(P<0.05),C+CFM-2组上述指标差异无统计学意义(P>0.05);与LPS+DMSO组比较,LPS+CFM-2组自发交替百分比升高,海马GluR2、Iba1和TNF-α表达下调,海马CA1区小胶质细胞数量减少(P<0.05)。结论GluR2可通过激活小胶质细胞,参与慢性神经炎症导致的小鼠认知功能障碍。Objective To evaluate the role of glutamate receptor 2(GluR2)in cognitive dysfunction induced by chronic neuroinflammation in mice.Methods Sixty adult male C57BL/6 mice,aged 8-10 weeks,weighing 18-25 g,were divided into 4 groups(n=15 each)using a random number table method:control+dimethyl sulfoxide(DMSO)group(group C+DMSO),control+AMPA receptor selective non-competitive antagonist CFM-2 group(group C+CFM-2),lipopolysaccharide(LPS)+DMSO group and LPS+CFM-2 group.In C+DMSO group and C+CFM-2 group,normal saline 0.2 ml was intraperitoneally injected every day for 10 consecutive days,and 10%DMSO 0.165 ml and CFM-233μmol/kg(diluted to 0.165 ml with 10%DMSO)were intraperitoneally injected,respectively,on the 10th day after injection of normal saline.In LPS+DMSO group and LPS+CFM-2 group,LPS 0.5 mg/kg(diluted to 0.2 ml with normal saline)was intraperitoneally injected every day for 10 consecutive days,and 10%DMSO 0.165 ml and CFM-233μmol/kg(diluted to 0.165 ml with 10%DMSO)were intraperitoneally injected,respectively,after LPS injection on the 10th day.The Y-maze test was performed at 48 h after the end of administration,then the animals were sacrificed,and the hippocampal tissues were taken for determination of the expression of GluR2,ionized calcium binding adapter molecule 1(Iba1),tumor necrosis factor-α(TNF-α)(by Western blot)and the number of microglia in hippocampal CA1 area(by immunofluorescence).Results Compared with group C+DMSO,the percentage of spontaneous alternation was significantly decreased,the expression of GluR2,Iba1 and TNF-αin hippocampus was up-regulated,the number of microglia in hippocampal CA1 area was increased(P<0.05),and no significant change was found in the parameters mentioned above in group LPS+DMSO(P>0.05).Compared with group LPS+DMSO,the percentage of spontaneous alternation was significantly increased,the expression of GluR2,Iba1 and TNF-αin hippocampus was down-regulated,and the number of microglia in hippocampal CA1 area was decreased in group LPS+CFM-2(P<0.05).Conclusions GluR2

关 键 词：受体 谷氨酸 认知功能障碍 神经炎症 

分 类 号：R749.1[医药卫生—神经病学与精神病学]