Chinese Medical Sciences Journal ›› 2018, Vol. 33 ›› Issue (4): 260-266.doi: 10.24920/003470

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  1. 1杭州市红十字会医院老年病科杭州 310003
    2杭州师范大学附属医院呼吸科杭州 330015 杭州市第一人民医院
    3呼吸科 杭州 310006
    4老年病科 杭州 310006
  • 收稿日期:2018-03-09 接受日期:2018-08-27 出版日期:2018-12-30 发布日期:2019-01-10
  • 通讯作者: 蔡萃

Combined Effects of Chronic Obstructive Pulmonary Disease and Depression on Spatial Memory in Old Rats

Cai Cui1,*(),Xu Changqing2,Jin Hualiang3,Li Bei4   

  1. 1 Department of Geriatrics, Hangzhou Red Cross Hospital, Hangzhou 310003, China
    2 Department of Respiratory, the Affiliated Hospital of Hangzhou Normal University,Hangzhou 330015, China
    3 Department of Respiratory, Hangzhou 310006, China
    4 Department of Geriatrics,Hangzhou First People’s Hospital, Hangzhou 310006, China;
  • Received:2018-03-09 Accepted:2018-08-27 Published:2018-12-30 Online:2019-01-10
  • Contact: Cai Cui


目的 老年慢性阻塞性肺疾病(Chronic obstructive pulmonary disease, COPD)患者常常合并抑郁状态,但目前对于老年人COPD伴抑郁的基础研究较少。本文探讨COPD伴抑郁对老年大鼠空间学习记忆能力的影响,将COPD、抑郁与衰老联系起来,以进一步了解老年COPD伴抑郁患者的疾病特点。 方法 将SD大鼠分为5组,分别为成年组、老年对照组、老年COPD组、老年抑郁组及老年COPD伴抑郁组。利用烟熏结合慢性轻度不可预见性应激(chronic unpredictable mild stress,CUMS)并孤养建立老年COPD伴抑郁大鼠模型。通过Morris水迷宫 (Morris water maze, MWM)试验检测大鼠的空间学习记忆能力,用黄嘌呤氧化酶法(Xanthinoxidase method)和硫代巴比妥酸反应法(TBAR)分别测定大鼠血清及海马组织中超氧化物歧化酶(SOD)的活性和丙二醛(MDA)的含量。比较各实验组与对照组各观测指标之间的差异。 结果 肺组织学、肺功能检测、敞箱实验及糖水消耗实验证实烟熏结合CUMS并孤养方法成功建立老年COPD伴抑郁大鼠模型。与老年对照组相比,老年COPD伴抑郁大鼠组在Morris水迷宫实验中到达平台的时间明显延长(LSD-t= -10.116, P=0.000),运动距离明显增加(LSD-t= -6.448, P=0.000);同时,老年COPD伴抑郁模型组中大鼠海马和血清中SOD的活性明显减少(LSD-t=2.629, P=0.014; LSD-t= 2.215, P=0.044),而MDA的含量显著增加((LSD-t= -2.140, P=0.042; LSD-t=-2.070,P=0.049)。 结论 慢性阻塞性肺疾病伴抑郁的老年大鼠空间学习记忆能力下降,其作用机制可能与氧化应激失衡有关。这一发现可能为临床老年COPD伴抑郁患者的治疗提供新的思路。

关键词: 慢性阻塞性肺疾病, 抑郁, 空间学习记忆, 衰老, 大鼠


Objective To investigate the combined effects of chronic obstructive pulmonary disease (COPD) and depression on spatial memory in old rats, aiming to better understand the comorbidity of the two diseases in geriatric patients. Methods The SD rats were assigned into five groups: adult control group (n=6), elderly control group (n=6), elderly COPD group (n=6), elderly depression group (n=6) and elderly COPD with depression group (n=6). Smoking and chronic unpredictable mild stress (CUMS) with solitary support were used to induce COPD model, depression model, respectively, and the both were applied for the comorbidity model. Learning and memory deficits were assessed by Morris water maze (MWM) test. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in serum and hippocampus tissue were determined by Xanthinoxidase method and Thiobarbituric acid reaction (TBAR) method, respectively. Results The results of pulmonary histology, lung function, open-field test and sucrose consumption demonstrated the comorbidity models of COPD and depression in elderly rats were successfully established using smoking and CUMS with solitary support. Compared with the elderly control group, the group of COPD with depression had obviously longer time of latency and longer travel distance to reach the platform in MWM test (LSD-t=-10.116, P=0.000; LSD-t=-6.448, P=0.000). The SOD activity in serum and hippocampus decreased significantly (LSD-t=2.629, P=0.014; LSD-t=2.215, P=0.044) and the MDA content in serum and hippocampus increased significantly (LSD-t=-2.140, P=0.042; LSD-t=-2.070, P=0.049) in elderly COPD with depression group. Conclusions COPD in comorbidity of depression could induce spatial memory deficit in old rats. The mechanisms might be related to the overloaded and free radical metabolic imbalance. These results suggest a potential therapeutic target for comorbidity of COPD and depression in geriatric patients.

Key words: chronic obstructive pulmonary disease, depression, spatial memory, aging, rats

基金资助: 浙江省自然科学基金(LQ12H27005)

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