术后认知功能障碍不同诊断标准的合理性探讨

目的:探讨目前国内外常用的三种术后认知功能障碍(Postoperative Cognitive Dysfunction,POCD)诊断标准的合理性。方法:以100名中青年健康志愿者为研究对象,采用神经心理学测验测定认知功能三次,第一次测定(T0)作为基础值,第二次测定1(T1)和第三次测定(T2)分别与第一次测定间隔3d和30d。分别按照自身对比法、标准差法和Z计分法检测健康人群中T1和T2时认知功能变化程度超出正常范围的人数。以检测结果服从正态分布为判断标准。结果:完成全程测量者80人。按照三种POCD诊断标准诊断,在T1时,认知功能提高人数分别是认知功能降低人数的30倍、17倍和1倍,在T2时分别是32倍、26倍和1.5倍。结论:在采用神经心理学方法研究POCD时,用Z计分法诊断POCD比自身对比法和标准差法更能准确地反映认知功能的客观变化。     

全身麻醉药物对术后认知功能的影响及可能机制的研究进展

术后认知功能障碍(postoperative cognitive dysfunction,POCD)是一种常见的术后并发症,好发于老年人。但其发病机制至今未能完全阐明,因此临床上缺少针对性的防治措施。近几年研究发现,麻醉药物是引起患者认知功能下降的重要原因之一。本文就全身麻醉药物对术后认知功能的影响及发生认知功能障碍的可能机制作论述,以期为POCD的防治提供新思路。     

不同麻醉方式对老年肺肿瘤患者术后早期认知功能的影响

目的:探讨不同麻醉选择对老年肺肿瘤术后患者早期认知功能的影响。方法:分析我院2011年3月至2013年3月老年肺肿瘤患者,分别有62例用全凭静脉麻醉和61例用静吸复合麻醉的麻醉方法,记录手术时间和麻醉时间,用MMSE量表进行认知功能评分,分别评定手术前1天和手术后出麻醉室时及1、3、5天患者的认知功能,并判断患者的POCD。结果:两组患者在手术时间和麻醉时间方面无统计学差异。与术前1天比较,全凭静脉麻醉组、静吸复合麻醉组出麻醉恢复室时、术后1 d时MMSE评分降低(P0.05);与术前1 d比较,两组在术后3天和7天时MMSE评分恢复正常(P0.05),两组患者之间的MMSE认知功能评分在术前、术后均无统计学差异(P0.05),出麻醉恢复室时,全凭静脉麻醉组发生POCD24例(39.34%),全凭静脉麻醉组发生25例(40.32%),两组发生率比较无统计学差异(P0.05);术后1天、3天、7天两组分别POCD的发生率比较均无统计学意义(P0.05)。结论:老年患者用全凭静脉麻醉、静吸复合麻醉不同麻醉方法对老年患者术后早期发生认知功能障碍的影响无统计学差异。     

老年患者全身麻醉术后认知功能障碍的影响因素分析

目的：探讨分析老年非心脏手术患者全身麻醉术后认知功能障碍(POCD)的影响因素。方法：选择我院80 例老年行非心脏手 术患者,所有患者均给予全身麻醉手术,于术前及术后1、3 d 分别使用简易智能状态检查法（MMSE）评估患者认知功能,同时记 录行不同手术种类患者POCD 发生率并分析其年龄、麻醉时间、术中出血量、并发症情况及受教育程度等指标与POCD发生的相 关性。结果：80 例患者POCD发生率为30.0%,且不同种类手术中的发生率比较差异无统计学意义（P＞0.05）;POCD 组术后1d MMSE 评分为较术前分明显下降,比较差异具有统计学意义（P＜0.05);POCD组术后3 d及非POCD 组术后1、3 d MMSE 评分与 术前比较差异无统计学意义（P＞0.05）;Logistic 回归分析显示,患者年龄、文化程度、麻醉持续时间≥ 3 h、术中出血量≥ 350 mL及 合并高血压与POCD的发生具有显著相关性（P＜0.05）。结论：行全麻手术患者术后POCD 发病率较高,且患者高龄、文化程度 低、高血压合并症及麻醉持续时间长等是引起POCD发生的重要影响因素。     

血清pNF-H、NSE、ESR与老年脊柱手术患者病情和术后认知功能的相关性研究

摘要 目的：研究老年脊柱手术患者血清神经丝蛋白H磷酸化亚型（pNF-H）、神经元特异性烯醇化酶（NSE）以及红细胞沉降率（ESR）水平与患者病情以及术后认知功能障碍发生的相关性。方法：选取2017年6月到2021年6月在我院进行脊柱手术的老年患者82例,根据病情严重程度分为脊髓未损伤组（n=35）、脊髓不完全损伤组（n=27）和脊髓完全损伤组（n=20）,根据术后是否发生认知功能障碍（POCD）分为认知功能障碍组（POCD组,n=30）和无认知功能障碍组（No-POCD组,n=52）。比较各组患者术前和术后1天、3天、7天血清pNF-H、NSE和ESR水平。结果：（1）脊髓未完全损伤组患者血清pNF-H、NSE和ESR均显著高于脊髓未损伤组患者,而均显著低于脊髓完全损伤组患者（P<0.05）;（2）No-POCD组和POCD组在性别、年龄、体重、BMI、手术时间以及术中失血量均具有可比性（P>0.05）;（3）POCD组患者术前和术后1天、3天、7天血清pNF-H、NSE和ESR水平均显著高于No-POCD组患者（P<0.05）。结论：老年脊柱手术患者血清pNF-H、NSE和ESR水平与患者病情以及术后认知功能障碍发生有关,术前及术后血清pNF-H、NSE和ESR水平升高可能增加老年脊柱手术患者术后认知功能障碍风险,检测血清pNF-H、NSE和ESR水平有助于评估老年手术患者病情和术后认知功能障碍发生风险。     

不同频率经皮穴位电刺激对妇科腹腔镜手术患者术后认知功能的影响

目的:评价不同频率经皮穴位电刺激对妇科腹腔镜手术患者术后认知功能的影响。方法:共选取择期行妇科腹腔镜手术患者80例,根据经皮穴位电刺激频率不同随机分成4组,N组患者20人不做经皮穴位电刺激,E1-E3组患者60人术中在内关、百会和风池穴使用经皮穴位电刺激,其中E1组经皮穴位电刺激频率为2Hz,E2组频率为100 Hz,E3组频率为2/100 Hz。观察四组患者术后认知功能障碍发生率之间的差异。结果:与N组比较E1-E3组POCD的发生率明显较低,差异具有统计学意义(P0.05)。但E1、E2、E3组患者POCD的发生率比较无明显差异(P0.05)。结论:经皮穴位电刺激内关、百会和风池穴可有效降低妇科腹腔镜手术患者术后认知功能障碍的发生率,但不同频率参数的刺激效果无明显差异。     

虎杖苷对老年小鼠术后认知功能障碍及海马氧化应激和神经炎症的影响

摘要 目的：探讨虎杖苷对老年小鼠术后认知功能障碍及海马氧化应激和神经炎症的影响。方法：C57BL/6J雄性老年小鼠,18月龄,体重24~28 g,随机分为4组：假手术组（Sham组）、术后认知功能障碍组（POCD组）、低剂量虎杖苷组（PD1组）、高剂量虎杖苷组（PD2组）。Sham组老年小鼠仅接受水合氯醛麻醉,不行外科手术;POCD组老年小鼠接受腹部手术以制备POCD老年动物模型;PD1组小鼠制备POCD模型,并于术后即刻、24 h和48 h分别腹腔注射低剂量虎杖苷25 mg/kg;PD2组小鼠制备POCD模型,并于术后即刻、24 h和48 h分别腹腔注射高剂量虎杖苷50 mg/kg。使用Morris水迷宫行为学实验评估老年小鼠术后认知功能,使用Western blot法检测术后小鼠海马Nrf2、HO-1、HMGB1、Iba-1蛋白水平,检测海马活性氧（ROS）、丙二醛（MDA）、超氧化物歧化酶（SOD）含量以反映术后海马氧化应激水平。结果：（1）与Sham组比较,POCD组老年小鼠术后逃离潜伏期显著增加（P<0.05）,穿越平台次数和目标象限停留时间下降（P<0.05）,海马Nrf2和HO-1蛋白表达水平明显降低（P<0.05）,氧化应激产物ROS和MDA含量增加（P<0.05）,抗氧化酶SOD活性降低（P<0.05）,Iba-1和HMGB1蛋白表达水平增加（P<0.05）;（2）与POCD组比较,PD1组和PD2组小鼠术后逃离潜伏期缩短（P<0.05）,穿越平台次数和目标象限停留时间增多（P<0.05）,海马Nrf2和HO-1蛋白表达水平升高（P<0.05）,ROS和MDA含量减少（P<0.05）,SOD活性增加（P<0.05）,Iba-1和HMGB1蛋白表达减少（P<0.05）。结论：虎杖苷可减轻老年小鼠术后认知功能损伤,缓解术后海马氧化应激和神经炎症,其机制可能与促进Nrf2/HO-1信号通路有关。     

右美托咪定对腰椎全麻手术患者术后疼痛及认知功能的影响

目的:探讨右美托咪定对腰椎全麻手术患者术后疼痛及认知功能的影响。方法:选择2014年3月~2015年12月在我院行腰椎全麻手术的84例患者为研究对象,按照随机数字表法分为对照组(42例)和试验组(42例),患者均常规给予芬太尼及顺式阿曲库铵麻醉诱导,试验组患者在麻醉诱导过程中给予右美托咪定静脉注射,对照组患者仅给予氯化钠注射液静脉注射。分别于术前(T0)、手术开始2 h(T2)、术后24 h(T24)检测血清肾上腺糖皮质激素,采用疼痛视觉模拟评分法(VAS)进行疼痛评定;采用简易智能精神状态量表(MMSE)于术后1d和2d进行认知状态评定,并计算术后认知功能障碍(POCD)发生率;同时观察患者不良反应发生情况。结果:试验组患者T2和T24时肾上腺糖皮质激素水平明显低于T0,T2时试验组患者肾上腺糖皮质激素水平明显低于对照组,差异有统计学意义(P0.05)。试验组患者T2时VAS评分明显低于对照组,差异有统计学意义(P0.05)。术后1d和2d时试验组患者的MMSE评分高于对照组,POCD发生率明显低于对照组;两组患者术后2d时MMSE评分高于术后1d,POCD发生率明显低于术后1d,差异均有统计学意义(P0.05)。两组患者均未见除POCD以外的不良反应。结论:右美托咪定有较强的抗氧化能力,可有效减轻腰椎全麻手术患者的疼痛程度,提高患者的认知功能。     

术后认知功能障碍新机制铁死亡的研究进展

铁死亡(ferroptosis)是一种铁依赖性的非凋亡的调节性细胞死亡(regulated cell death, RCD)方式,其特点是细胞内脂质过氧化产物和活性氧(reactive oxygen species, ROS)堆积。麻醉手术后患者因中枢神经系统损伤出现认知功能障碍的具体机制仍然不清。近些年,铁死亡在术后认知功能障碍(postoperative cognitive dysfunction, POCD)的发病机制中备受关注,且与神经炎症、线粒体能量代谢、自噬等致病机理密切相关。本文就铁死亡的生物学特征和功能以及在POCD研究中的进展进行综述,以期为预防和治疗该类神经系统疾病提供最新的有价值的信息。     

海马Sirt1在高压氧预处理改善异氟醚诱导老龄小鼠认知功能障碍中的作用

摘要 目的：通过shRNA抑制沉默信息调节因子1（sirtuin 1,Sirt1）基因表达,研究Sirt1在高压氧预处理改善异氟醚（isoflurane,ISO）诱导小鼠认知功能障碍中的作用及其对小鼠海马BDNF、GDNF基因表达的影响。方法： 将64只C57雄性小鼠随机分为假手术组（Sham组）、高压氧组（HBO组）、异氟醚组（ISO组）、高压氧预处理+异氟醚组（HBO + ISO组）;以及对照组（NS组）、Sirt1抑制组（sh-Sirt1组）、对照+高压氧预处理组（NS + HBO组）和Sirt1抑制+高压氧预处理组（sh-Sirt1 + HBO组）,每组8只。经慢病毒转染以及ISO末次暴露24小时后进行认知功能测试（Morris水迷宫测试）,随后处死小鼠,利用实时荧光定量聚合酶链反应（RT-qPCR）检测海马BDNF和GDNF的mRNA表达情况。结果：（1）异氟醚可以导致明显的认知功能障碍,与Sham组相比,ISO组靶象限探索时间百分比显著减低（P<0.01）,ISO组小鼠海马BDNF和GDNF mRNA表达水平显著下降（P<0.01）。（2）高压氧预处理可以改善POCD小鼠的认知功能障碍,ISO + HBO组靶象限探索时间百分比显著高于ISO组（P<0.05）,ISO + HBO组小鼠海马BDNF（P<0.05）和GDNF（P<0.01）mRNA表达水平显著升高。（3）高压氧预处理可以显著增加POCD小鼠海马BDNF（P<0.01）和GDNF（P<0.05）mRNA表达水平,慢病毒介导shRNA靶向下调Sirt1可以逆转高压氧预处理对POCD小鼠海马BDNF（P<0.05）和GDNF（P<0.01）mRNA表达水平的改变。结论：高压氧预处理是治疗POCD的有效方法,Sirt1可能是POCD治疗的潜在分子靶点。     

MicroRNA-572 Improves Early Post-Operative Cognitive Dysfunction by Down-Regulating Neural Cell Adhesion Molecule 1

Post-operative cognitive dysfunction (POCD) is a commonly-seen postoperative complication in elderly patients. However, the underlying mechanisms of POCD remain unclear. miRNAs, which are reported to be involved in the pathogenesis of the nervous system diseases, may also affect POCD. In this study, miRNA microarray technology was used to analyze the circulating miRNA expression profile of POCD patients. Among the altered miRNAs, miR-572 had the greatest decrease, which was also verified in vivo in rat POCD model. Further analysis found that miR-572 could regulate the expression of NCAM1 in the hippocampal neurons and interfering miR-572 expression could facilitate the restoration of cognitive function in vivo. Moreover, clinical correlation analysis found that the miR-572 expression was associated with the incidence of POCD. Collectively, miR-572 is involved in the development and restoration of POCD and it may serve as a biological marker for early diagnosis of POCD.     

术后认知功能障碍发病机制的研究进展

术后认知功能障碍(POCD)是术前无精神障碍的患者受围术期各种因素的影响,在术后出现的神经并发症,表现为焦虑、认识障碍、记忆受损和人格改变。随着医疗技术水平的不断提高,围术期死亡率及手术和麻醉并发症大大降低,但POCD发病率未见明显改善,严重影响患者预后康复及远期生存质量,引起很多学者的关注。认识和分析POCD,成为当今麻醉管理的重要课题。POCD是多种影响因素共同作用的结果,评估方法较多且相对主观,没有标准统一的评估、预防、诊断及治疗方法,目前虽已有大量动物实验及临床研究,但其发病机制仍不明确。因此全面认识和分析POCD发病机制的进展情况,进一步探讨其预防和治疗方法,具有重要的临床和社会意义。     

Postoperative Cognitive Dysfunction is Correlated with Urine Formaldehyde in Elderly Noncardiac Surgical Patients

Post-operative cognitive dysfunction (POCD), especially in elderly patients, has been reported in many studies. Although increasing age, duration of anesthesia, postoperative infections, and respiratory complications were regarded as the risk factors for POCD, no extracerebral diagnostic biomarkers have been identified as indicators of POCD. Ninety-five patients, ages 65-80?years, scheduled for major orthopedic or abdominal surgery were enrolled. Twenty-two patients aged between 20 and 40?years undergoing the same procedures served as controls. Subjects received neuropsychological tests one-day prior and one week post procedure.?To determine the presence of POCD, the criteria were used as described in most previous studies. Morning urine samples were obtained one day before surgery and on day 1, day 2 and day 7 post operatively. Urine formaldehyde was determined with high-performance liquid chromatography. The urine formaldehyde level of all patients with and without POCD increased on the first 2?days after surgery. But the formaldehyde concentration (on day 7) in patients with POCD was significantly higher than that in patients without POCD (p?相似文献   

Necrostatin-1 Against Sevoflurane-Induced Cognitive Dysfunction Involves Activation of BDNF/TrkB Pathway and Inhibition of Necroptosis in Aged Rats

Postoperative cognitive dysfunction (POCD) induced by anesthesia or surgery has become a common complication in the aged population. Sevoflurane, a clinical inhalation anesthetic, could stimulate calcium overload and necroptosis to POCD. In addition, necroptosis inhibitor necrostatin-1 (Nec-1) alleviated cognitive impairment caused by multiple causes, including postoperative cognitive impairment. However, whether Nec-1 exerts a neuroprotective effect on POCD via calcium and necroptosis remains unclear. We anesthetized Sprague–Dawley rats with sevoflurane to construct the POCD model and to explore the mechanism underlying neuroprotective effects of Nec-1 in POCD. Rats were treated with Nec-1 (6.25 mg/kg) 1 h prior to anesthesia. Open field test and Morris water maze were employed to detect the cognitive function. In this study, rats exposed to sevoflurane displayed cognitive dysfunction without changes in spontaneous activity; however, the sevoflurane-induced POCD could be relieved by Nec-1 pretreatment. Nec-1 decreased sevoflurane-induced calcium overload and calpain activity in the hippocampus. In addition, Nec-1 alleviated the expression of p-RIPK1, RIPK1, p-RIPK3, RIPK3, p-MLKL and MLKL. Furthermore, Nec-1 remarkably increased BDNF and p-TrkB/TrkB expression in the hippocampus of aged rats. Ultimately, our research manifests evidence that Nec-1 may play a neuroprotective role against sevoflurane-induced cognitive impairment via the increase of BDNF/TrkB and suppression of necroptosis-related pathway.

     

Sarm1 is Essential for Anesthesia-Induced Neuroinflammation and Cognitive Impairment in Aged Mice

Postoperative cognitive dysfunction (POCD) is a common phenomenon among elderly patients with unclear etiology. Sterile alpha and TIR motif-containing 1 (Sarm1) plays important roles in neuroinflammation and cognitive function, and activates Calpain which has been shown to promote POCD through TrkB cleavage. This study aims to test the hypothesis that Sarm1 is involved in POCD through regulating Calpain activity. Wild type and Sarm1 knock out mice were exposed to isoflurane. Mouse cognitive function was determined by Morris water maze test. Neuroinflammation was determined by Iba1 and GFAP protein levels and mRNA expression of proinflammatory cytokines. Calpain activation was determined by αII-spectrin degradation and TrkB cleavage. Mitogen-activated protein kinase (MAPK) signaling was determined by c-Jun N-terminal kinase and cJun phosphorylation both in vivo and in vitro by Western blot and immunofluorescence staining. We found that Sarm1 deletion suppressed isoflurane induced cognitive impairment and neuroinflammation. Deletion of Sarm1 inhibited isoflurane induced αII-spectrin degradation and TrkB cleavage, which indicates suppression of Calpain activation. Finally, deletion of Sarm1 suppressed isoflurane induced MAPK signaling both in vivo and in vitro. Our findings suggest that isoflurane anesthesia induced cognitive impairment is prevented by Sarm1 deletion in mice, making Sarm1 a potent therapeutic target for treating or preventing POCD.

     

Protective Effects of Edaravone in Adult Rats with Surgery and Lipopolysaccharide Administration-Induced Cognitive Function Impairment

Postoperative cognitive dysfunction (POCD) is a clinical syndrome characterized by cognitive declines in patients after surgery. Previous studies have suggested that surgery contributed to such impairment. It has been proven that neuroinflammation may exacerbate surgery-induced cognitive impairment in aged rats. The free radical scavenger edaravone has high blood brain barrier permeability, and was demonstrated to effectively remove free radicals from the brain and alleviate the development of POCD in patients undergoing carotid endarterectomy, suggesting its potential role in preventing POCD. For this reason, this study was designed to determine whether edaravone is protective against POCD through its inhibitory effects on inflammatory cytokines and oxidative stress. First, Sprague Dawley adult male rats were administered 3 mg/kg edaravone intraperitoneally after undergoing a unilateral nephrectomy combined with lipopolysaccharide injection. Second, behavioral parameters related to cognitive function were recorded by fear conditioning and Morris Water Maze tests. Last, superoxide dismutase activities and malondialdehyde levels were measured in the hippocampi and prefrontal cortex on postoperative days 3 and 7, and microglial (Iba1) activation, p-Akt and p-mTOR protein expression, and synaptic function (synapsin 1) were also examined 3 and 7 days after surgery. Rats that underwent surgery plus lipopolysaccharide administration showed significant impairments in spatial and working memory, accompanied by significant reductions in hippocampal-dependent and independent fear responses. All impairments were attenuated by treatment with edaravone. Moreover, an abnormal decrease in superoxide dismutase activation, abnormal increase in malondialdehyde levels, significant increase in microglial reactivity, downregulation of p-Akt and p-mTOR protein expression, and a statistically significant decrease in synapsin-1 were observed in the hippocampi and prefrontal cortices of rats at different time points after surgery. All mentioned abnormal changes were totally or partially reversed by edaravone. To our knowledge, few reports have shown greater protective effects of edaravone on POCD induced by surgery plus lipopolysaccharide administration from its anti-oxidative stress and anti-inflammatory effects, as well as maintenance of Akt/mTOR signal pathway activation; these might be closely related to the therapeutic effects of edaravone. Our research demonstrates the potential use of edaravone in the treatment of POCD.     

Effects of miR-190a-3p on Sevoflurane-induced postoperative cognitive dysfunction (POCD)

Postoperative cognitive dysfunction (POCD) is regularly observed in patients postsurgery due to the usage of anesthetics, including Sevoflurane. Research has confirmed the participation of oxidative stress (OS) and inflammation in the pathogenesis of POCD. Recently, the potential therapeutic function of miR-190a-3p against cognitive dysfunction has been reported. However, its role and mechanism in POCD are unclear. Our study will focus on the protective property and mechanism of miR-190a-3p on POCD to seek potential biomarkers and treatment targets for POCD. The animal model of POCD was constructed by the injection of Sevoflurane, followed by the administration of mimic negative control and miR-190a-3p. MiR-190a-3p was found to be downregulated in POCD rats. Declined time to explore the platform, swimming distance, and times that rats crossed the platform were observed in POCD rats, accompanied by increased secretion of proinflammatory cytokines, elevated malondialdehyde levels, repressed superoxide dismutase activity, and decreased levels of reduced glutathione, all of which were dramatically reversed by miR-190a-3p. Furthermore, the downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and activation of toll-like receptor 4/nuclear factor-κB signaling were observed in POCD rats, which were greatly rescued by miR-190a-3p. Lastly, the Nrf2 luciferase activity and Nrf2 levels in HT22 cells were extremely improved by miR-190a-3p. Collectively, miR-190a-3p alleviated Sevoflurane-induced POCD in rats by repressing OS and inflammation.     

AMPKα1 overexpression improves postoperative cognitive dysfunction in aged rats through AMPK-Sirt1 and autophagy signaling

Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients who undergo surgery involving anesthesia. Its underlying mechanisms remain unclear. Autophagy plays an important role in the damage and repair of the nervous system and is associated with the development of POCD. Using a rat model, adenosine monophosphate-activated protein kinase α1 (AMPKα1), an important autophagy regulator, was found to be significantly downregulated in rats with POCD that was induced by sevoflurane anesthesia or by appendectomy. Overexpression of AMPKα1-ameliorated POCD, as indicated by decreased escape latencies and increased target quadrant swimming times, swimming distances, and platform crossing times during Morris water maze tests. AMPKα1 overexpression activated autophagy signals by increasing the expression of light chain 3 II (LC3-II) and Beclin1 and decreasing the expression of p62 in the hippocampus of rats with POCD. Moreover, blocking autophagy by 3-methyladenine partly attenuated AMPKα1-mediated POCD improvement. Furthermore, overexpression of AMPKα1 could upregulate the expression of p-AMPK and Sirt1 in the hippocampus of rats with POCD. Intriguingly, inhibiting AMPK signals via Compound C effectively attenuated AMPKα1-mediated POCD improvement, concomitant with the downregulation of p-AMPK, Sirt1, LC3-II, and Beclin1 and the upregulation of p62. We thus concluded that overexpression of AMPKα1 can improve POCD via the AMPK-Sirt1 and autophagy signaling pathway.