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

作　　者：刘露玉 公茂伟 廖国松 赵维星 傅强 LIU Luyu;GONG Maowei;LIAO Guosong;ZHAO Weixing;FU Qiang(Department of Anesthesiology,First Medical Center,Chinese PLA General Hospital,Beijing 100853,China;Graduate School,Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]中国人民解放军总医院第一医学中心麻醉科,北京100853 [2]中国人民解放军总医院研究生院,北京100853

出　　处：《南方医科大学学报》2025年第4期725-735,共11页Journal of Southern Medical University

基　　金：国家自然科学基金(82071178,82201333)。

摘　　要：目的探索高血压与术后认知功能障碍的关系及其可能的机制。方法采用七氟烷麻醉下颈动脉暴露手术构建术后学习记忆损伤动物模型,将12周龄自发性高血压大鼠(SHR)和正常血压对照Wistar-Kyoto大鼠(WKY)根据是否手术分为4组,即WKY+CON组、WKY+SUR组、SHR+CON组、SHR+SUR组,8只/组。行为学测试评估大鼠术后认知变化;生物学检测炎症反应和氧化应激水平。结果高血压大鼠术后发生了明显学习记忆损伤,表现为新物体识别指数明显降低(P<0.05);场景相关和声音相关恐惧测试僵直时间均缩短(P<0.05)。与WKY大鼠相比,SHR大鼠术后海马线粒体UCP2表达和膜电位明显降低,而ATP水平显著升高(P<0.05);血清活性氧、IL-6、IL-1β炎症因子升高(P<0.05);此外,SHR大鼠星形胶质细胞过度激活,神经元Nissl染色阳性细胞个数明显减少,差异均有统计学意义(P<0.05)。结论高血压可加重大鼠术后学习记忆损伤,这可能与UCP2介导的线粒体功能障碍和氧化应激损伤,进一步导致星型胶质细胞过度活化和神经元损伤有关。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-1βand TNF‑αwere 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 

分 类 号：R614[医药卫生—麻醉学]