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IR@PKUHSC  > 北京大学第三临床医学院  > 麻醉科  > 期刊论文
学科主题: 临床医学
题名:
Prophylactic angiotensin type 1 receptor antagonism confers neuroprotection in an aged rat model of postoperative cognitive dysfunction
作者: Li, Zhengqian1; Cao, Yiyun1; Li, Lunxu1; Liang, Yaoxian2; Tian, Xiaosheng3,4,5; Mo, Na6; Liu, Yajie1; Li, Min1; Chui, Dehua3,4,5; Guo, Xiangyang1
关键词: Postoperative cognitive dysfunction ; Renin-angiotensin system ; Angiotensin II receptor type 1 ; Blood-brain barrier ; Neuroinflammation
刊名: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
发表日期: 2014-06-20
DOI: 10.1016/j.bbrc.2014.04.153
卷: 449, 期:1, 页:74-80
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]: Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]: BLOOD-BRAIN-BARRIER ; ALZHEIMERS-DISEASE ; AT(1) RECEPTOR ; DECLINE ; ACTIVATION ; BLOCKERS ; MICE ; PERMEABILITY ; CANDESARTAN ; IMPAIRMENT
英文摘要:

Postoperative cognitive dysfunction (POCD) is a common geriatric complication, although its exact neuropathogenesis remains elusive. Blockers of the renin-angiotensin system (RAS) ameliorate cognitive deficits in inflammatory brain disorders, with its effects on POCD not yet fully elucidated. The aim of the present study was to investigate regulation of the brain RAS and the effect of angiotensin II receptor type 1 (AT1) inhibition on surgery-induced cognitive impairment in a well-established rat POCD model. We observed upregulation of angiotensin II protein expression and AT1 subtype B transcript levels in the hippocampus after laparotomy, suggesting surgical stress activates the hippocampal RAS in aged rats. Chronic pretreatment with 0.1 mg/kg/day candesartan, an AT1 antagonist, significantly attenuated surgery-induced cognitive deficits in the Morris water maze task without altering blood pressure. Candesartan also decreased hippocampal blood-brain barrier (BBB) permeability. Concomitant with these functional benefits, we observed significant inhibition of hippocampal neuroinflammation, evidenced by decreased glial reactivity and phosphorylation of the NF-kappa B p65 subunit, as well as marked reductions in interleukin-1 beta, tumor necrosis factor-alpha, and cyclooxygenase-2. Our results are the first to show that activation of the brain RAS after surgery contributes to POCD in aged rats. Chronic treatment with low doses of candesartan may elicit blood pressure-independent neuroprotective effects in POCD by improving BBB function and promoting resolution of neuroinflammation. (C) 2014 Elsevier Inc. All rights reserved.

语种: 英语
所属项目编号: 81371205 ; 2012CB911004 ; 20110001110008
项目资助者: National Natural Science Foundation of China ; National Basic Research Program of China (973 Program) ; Doctoral Fund of the Ministry of Education of China
WOS记录号: WOS:000337990700013
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52800
Appears in Collections:北京大学第三临床医学院_麻醉科_期刊论文

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作者单位: 1.Peking Univ, Hosp 3, Dept Anesthesiol, Beijing 100191, Peoples R China
2.Peking Univ, Hosp 3, Dept Nephrol, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Neurosci Res Inst, Beijing 100191, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Dept Neurobiol, Key Lab Neurosci,Minist Educ, Beijing 100191, Peoples R China
5.Peking Univ, Hlth Sci Ctr, Minist Publ Hlth, Beijing 100191, Peoples R China
6.Chinese Acad Med Sci, Canc Inst & Hosp, Beijing 100021, Peoples R China

Recommended Citation:
Li, Zhengqian,Cao, Yiyun,Li, Lunxu,et al. Prophylactic angiotensin type 1 receptor antagonism confers neuroprotection in an aged rat model of postoperative cognitive dysfunction[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2014,449(1):74-80.
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