南方医科大学学报2025，Vol.45Issue(4)：725-735,11.DOI:10.12122/j.issn.1673-4254.2025.04.07
高血压通过UCP2下调介导的线粒体功能障碍加重大鼠术后学习记忆损伤
Hypertension exacerbates postoperative learning and memory impairment in rats possibly due to UCP2 downregulation-mediated mitochondrial dysfunction
摘要
Abstract
Objective To explore the correlation of hypertension with postoperative cognitive dysfunction and its possible mechanism.Methods Twelve-week-old spontaneously hypertensive rats(SHRs)and Wistar-Kyoto(WKY)rats were both randomized into control group and surgical group(n=8).In the latter group,the rats received carotid artery exposure surgery under sevoflurane anesthesia to establish models of postoperative learning and memory impairment.Postoperative cognitive function changes of the rats were evaluated using behavioral tests.The hippocampus of the rats were collected for determining ATP level and mitochondrial membrane potential(MMP)and for detecting expressions of UCP2 and astrocyte markers(GFAP and NOX4)using Western blotting and immunofluorescence staining.Serum levels of ROS,IL-6,IL-1β and TNF-α were detected using ELISA.Nissl staining was used to examine hippocampal neuronal loss in the CA1 region.Results The SHRs exhibited exacerbated learning and memory deficits following the surgery as shown by significantly reduced performance in novel object recognition tests and context-related and tone-related fear conditioning experiments.Compared with WKY rats,the SHRs had significantly decreased mitochondrial UCP2 expression and MMP in the hippocampus,increased hippocampal ATP level,and markedly increased serum levels of ROS and inflammatory factors,showing also increased activation of hippocampal astrocytes and microglia and reduced number of neurons positive for Nissl staining.Conclusion Hypertension can exacerbate major postoperative learning and memory impairment in rats possibly as a result of UCP2-mediated mitochondrial dysfunction and oxidative stress damage,which further leads to astrocyte overactivation and neuronal damage.关键词
术后认知功能障碍/自发性高血压大鼠/解偶联蛋白2/颈动脉暴露/高血压/线粒体Key words
postoperative cognitive dysfunction/spontaneously hypertensive rats/uncoupling protein 2/carotid artery exposure surgery/hypertension/mitochondria引用本文复制引用
刘露玉,公茂伟,廖国松,赵维星,傅强..高血压通过UCP2下调介导的线粒体功能障碍加重大鼠术后学习记忆损伤[J].南方医科大学学报,2025,45(4):725-735,11.基金项目
国家自然科学基金(82071178,82201333) Supported by National Science Foundation of China(82071178,82201333). （82071178,82201333）
