中脑腹侧被盖区多巴胺转运蛋白的变化对老年大鼠术后认知功能的影响  

Effects of dopamine transporter changes in the ventral tegmental area of the midbrain on postoperative cognitive function in elderly rats

作　　者：许珂 郭佳 葛明月 殷姜文 殷洁婷 张晗 李燕[2] XU Ke;GUJia;GE Mingyue;YIN Jiangwen;YIN Jieting;ZHANG Han;LI Yan(School of Medicine,Shihezi University,Shihezi,Xinjiang 832002,China;Department of Anesthesiology,the First Affiliated Hospital,School of Medicine,Shihezi University,Shihezi,Xinjiang 832008,China)

机构地区：[1]石河子大学医学院,新疆石河子832002 [2]石河子大学医学院第一附属医院,新疆石河子832002

出　　处：《石河子大学学报（自然科学版）》2021年第3期359-364,共6页Journal of Shihezi University(Natural Science)

基　　金：国家自然科学基金项目(81860209)。

摘　　要：目的研究中脑腹侧被盖区(VTA)多巴胺转运蛋白的变化与老年大鼠术后发生认知功能障碍之间的关系。方法将50只大鼠随机分为空白组、假手术组、PND模型组、多巴胺转运蛋白敲低AAV·DAT·RNAi组、多巴胺转运蛋白敲低阴性对照AAV·NC组,每组10只。模型组大鼠进行丙泊酚全麻下脾切除手术;AAV干预大鼠预先经脑立体定位仪显微靶向注射AAV·DAT·RNAi或AAV·NC至VTA核团;假手术组大鼠输注丙泊酚。采用Morris水迷宫及条件恐惧实验判断大鼠认知功能损伤程度;免疫荧光染色观察VTA区及海马CA1区DAT、α-synuclein(α-syn)、β-Amyloid1-42(Aβ1-42)的蛋白定位及表达情况;Western blot法检测海马α-synuclein(α-syn)、β-Amyloid1-42(Aβ1-42)的蛋白含量,比较各组间蛋白含量的差异。结果与空白组比较,PND模型组大鼠行为学表现出明显的认知功能减退;海马CA1区α-syn、Aβ1-42蛋白含量明显升高(P<0.05)。与PND模型组相比,AAV·DAT·RNAi组大鼠行为学显示认知功能减退改善;AAV·DAT·RNAi组VTA区多巴胺转运蛋白含量明显降低;海马CA1区α-syn、Aβ1-42蛋白含量明显降低(P<0.05)。结论VTA区多巴胺转运蛋白参与了老年大鼠认知功能障碍,并且VTA区DAT变化对老年大鼠术后认知功能的影响可能与调控海马区α-syn、Aβ1-42蛋白聚集有关。Objective To investigate the relationship between the changes of dopamine transporters in the ventral tegmental area(VTA)of the midbrain and postoperative cognitive dysfunction in elderly rats.Methods 50 SD rats were randomly divided into Normal group,Sham group,PND model group,Dopamine transporter knockdown AAV·DAT·RNAi group,and Dopamine transporter knockdown negative control AAV·NC group,with 10 rats in each group.Rats in group PND model underwent splenectomy with propofol general anesthesia.The group AAV·DAT·RNAi was injected with adenovirus under stereotactic technique.Group AAV·NC was injected with control adenovirus.Rats in group Sham were infused with propofol.Morris water maze and conditioned fear experiment were used to determine the degree of cognitive damage in rats.Immunofluorescence was performed to observe the protein localization and expression of DAT,α-synuclein、β-Amyloid1-42 in the VTA region and the hippocampal CA1 region.The protein content ofα-synuclein andβ-Amyloid1-42 in the hippocampus was detected by Western blot,and the protein content differences among the groups were compared.Results Compared with group Normal,the rats of group PND model showed obvious cognitive decline,and the contents ofα-synuclein andβ-Amyloid1-42 proteins in the hippocampal CA1 region were significantly increased(P<0.05).Compared with group PND model,the cognitive decline of group AAV·DAT·RNAi was improved and the content of dopamine transporter in VTA region decreased significantly;The protein contents ofα-syn and Aβ1-42 in hippocampus CA1 region were significantly decreased(P<0.05).Conclusions Dopamine transporter in VTA region is involved in cognitive dysfunction in elderly rats,and the effect of DAT changes in VTA region on postoperative cognitive function in elderly rats may be related to the regulation ofα-syn and Aβ1-42 protein aggregation in hippocampus.

关 键 词：围术期神经认知障碍 中脑腹侧被盖区 多巴胺转运蛋白 海马 Α-SYNUCLEIN β-Amyloid1-42 

分 类 号：R641[医药卫生—外科学]