etomidate

依托咪酯
  • 文章类型: Journal Article
    依托咪酯可在麻醉诱导过程中诱发肌阵颤,发生率为50〜85%。地塞米松,作为一种长效合成糖皮质激素,具有神经保护作用。然而,地塞米松对依托咪酯诱导的肌阵颤的影响尚不确定.
    成年雄性Sprague-Dawley大鼠随机分配接受依托咪酯(1.5mg/kg)加地塞米松(4mg/kg)(依托咪酯加地塞米松组)或依托咪酯(1.5mg/kg)加相同体积的生理盐水(NS)(依托咪酯加NS组)。平均行为得分,记录局部场电位和肌张力,以探讨地塞米松对依托咪酯诱导的肌阵挛症的影响.液相色谱-串联质谱系统(LC-MS/MS)定量实时聚合酶链反应(qRT-PCR),应用蛋白质印迹法分析谷氨酸和γ-氨基丁酸(GABA)的水平,兴奋性氨基酸转运蛋白(EAATs)的mRNA和蛋白表达,麻醉后不同时间点血浆皮质酮水平。
    与依托咪酯加NS治疗相比,依托咪酯+地塞米松治疗显著降低了给药后1,3,4和5分钟的平均行为评分;波纹波分析中的峰值功率谱密度(PSD)(p=0.0197);新皮质中的谷氨酸水平(p=0.0139).然而,与依托咪酯加NS相比,依托咪酯加地塞米松增加了EAAT1(p=0.0207)和EAAT2(p=0.0022)的新皮质蛋白的表达,并在4h时加重了皮质酮的抑制(p=0.0019),5小时(p=0.0041),和给药后6小时(p=0.0009)。
    地塞米松可以减轻肌阵挛症,抑制谷氨酸的积累,并逆转由依托咪酯诱导的新皮质中EAAT的抑制,而反过来加重依托咪酯诱导的肾上腺抑制。
    UNASSIGNED: Etomidate can induce myoclonus with an incidence of 50 ~ 85% during anesthesia induction. Dexamethasone, as a long-acting synthetic glucocorticoid, has neuroprotective effects. However, the effects of dexamethasone on the etomidate-induced myoclonus remain uncertain.
    UNASSIGNED: Adult male Sprague-Dawley rats were randomly assigned to receive etomidate (1.5 mg/kg) plus dexamethasone (4 mg/kg) (etomidate plus dexamethasone group) or etomidate (1.5 mg/kg) plus the same volume of normal saline (NS) (etomidate plus NS group). The mean behavioral scores, local field potentials and muscular tension were recorded to explore the effects of dexamethasone on etomidate-induced myoclonus. Liquid chromatography coupled with tandem mass spectrometric system (LC-MS/MS), quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting were applied to analyze the levels of glutamate and γ-aminobutyric acid (GABA), the mRNA and protein expression of excitatory amino acid transporters (EAATs), and plasma corticosterone levels at different time points after anesthesia.
    UNASSIGNED: Compared with the etomidate plus NS treatment, the etomidate plus dexamethasone treatment significantly decreased the mean behavioral score at 1, 3, 4, and 5 min after administration; the peak power spectral density (PSD) (p = 0.0197) in the analysis of ripple waves; and the glutamate level (p = 0.0139) in the neocortex. However, compared with etomidate plus NS, etomidate plus dexamethasone increased the expression of the neocortical proteins of EAAT1 (p = 0.0207) and EAAT2 (p = 0.0022) and aggravated the inhibition of corticosterone at 4 h (p = 0.0019), 5 h (p = 0.0041), and 6 h (p = 0.0009) after administration.
    UNASSIGNED: Dexamethasone can attenuate the myoclonus, inhibit the glutamate accumulation, and reverse the suppression of EAATs in the neocortex induced by etomidate following myoclonus, while conversely aggravating etomidate-induced adrenal suppression.
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  • 文章类型: Journal Article
    雷马唑仑是一种新型的短效苯二氮卓类药物,用于镇静和全身麻醉。本研究旨在评估在接受诊断性胃肠镜检查的老年患者中使用苯磺酸瑞咪唑安定的有效性和安全性。
    将120名年龄在60-75岁的患者随机分为两组。采用瑞芬太尼0.3μg/kg镇痛。患者分别给予苯磺酸瑞米唑仑7mg(R组)或依托咪酯0.1mg/kg联合1%丙泊酚0.5mg/kg(EP组)进行诱导,根据需要给予补充重复剂量。一些时间指标,生命体征,对不良事件进行了评估.比较患者的Mini-cog评分和康复问卷。
    与EP组相比,R组诱导时间稍长(1.50VS1.15分钟)(P<0.05),在麻醉后监护病房(PACU)中花费的时间较短(15.17VS17.40分钟)(P<0.05)。与EP组相比,在T15和T25时间点,R组SBP较低,T2、T3、T5时心率较高(P<0.05)。术后Mini-Cog评分较高(2.83VS2.58)(P<0.05)。EP组呼吸不良事件发生率高于R组(18.3%VS5.0%,P<0.05)。R组最常见的不良事件是打嗝。R组患者的镇静满意率和健忘症程度均较高(66.7%VS11.7%)(P<0.05),对患者24小时内生活的影响较低(12.0%VS30.5%)(P<0.05)。
    苯磺酸瑞马唑仑的安全性和有效性不亚于依托咪酯联合丙泊酚,使其成为ASAI-II老年患者在胃肠内窥镜检查期间镇静的安全选择,但是应该注意监控打嗝的发生。
    UNASSIGNED: Remimazolam is a novel short-acting benzodiazepine used for sedation and general anesthesia. This study aimed to evaluate the efficacy and safety of remimazolam besylate in elderly patients who underwent diagnostic gastrointestinal endoscopy.
    UNASSIGNED: A total of 120 patients aged 60-75 years were randomly allocated to one of two groups. Remifentanil 0.3μg/kg was used for analgesia. Patients were administered remimazolam besylate 7 mg (R group) or etomidate 0.1 mg/kg combined with 1% propofol 0.5 mg/kg (EP group) for induction, supplemental repeated doses were given as needed. Some time metrics, vital signs, adverse events were evaluated. Patients\' Mini-cog score and recovery questionnaires were compared.
    UNASSIGNED: Compared to the EP group, the induction time was slightly longer in the R group (1.50 VS 1.15 minutes) (P<0.05), the time spent in the post-anesthesia care unit (PACU) was shorter (15.17 VS 17.40 minutes) (P<0.05). Compare with EP group, SBP was lower in R group at T15 and T25 time point, but heart rate was higher in T2, T3, T5 (P< 0.05). The Mini-Cog score was higher after the procedure (2.83 VS 2.58) (P<0.05). The incidence of respiratory adverse events was higher in the EP group than R group (18.3% VS 5.0%, P < 0.05). The most common adverse event in R group was hiccups. The sedation satisfaction rate and degree of amnesia were higher in the R group (66.7% VS 11.7%) (P < 0.05), and the effect on patient\'s life within 24 hours was lower (12.0% VS 30.5%) (P < 0.05).
    UNASSIGNED: The safety and efficacy of remimazolam besylate are not inferior to those of etomidate combined with propofol, rendering it a safe option for sedation during gastrointestinal endoscopy in ASA I-II elderly patients, but care should be taken to monitor the occurrence of hiccups.
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  • 文章类型: Journal Article
    依托咪酯作为非巴比妥镇静剂,具有中心抑制作用和成瘾,由于当今的滥用趋势,在一些国家已被列为管制药物。因此,快速、灵敏地检测依托咪酯具有重要意义。在这项工作中,首次报道了一种基于铜纳米簇(CuNCs)和分子印迹聚合物(MIPs)的新型荧光传感探针(CuNCs@MIPs)。CuNC是使用聚(乙烯基吡咯烷酮)作为模板和抗坏血酸作为还原剂的环境友好合成的。用分子印迹技术功能化后,CuNCs@MIPs探针在靶向依托咪酯的表面上具有特殊的结合腔,导致荧光强度迅速下降,这证实了它具有出色的灵敏度,选择性和稳定性。在最优条件下,荧光传感探针在10-500ng/ml范围内对依托咪酯呈高精度线性关系,检出限为10ng/ml,整个检测过程在10min内完成。这种传感方法也已应用于实际样品的检测,在电子烟液和尿液中仍然表现出优异的可行性。更重要的是,与以前的方法相比,这种荧光传感方法具有快速、简单,易于操作。总的来说,CuNCs@MIPs传感探针具有良好的荧光特性和简单的合成策略,在依托咪酯的检测和应用方面显示出巨大的潜力。
    Etomidate as a non-barbiturate sedative, has central inhibitory effect and addiction and has been listed as a controlled drug in some countries due to the abusing trend nowadays. Therefore, rapid and sensitive detection of etomidate is of great significance. In this work, a novel fluorescent sensing probe (CuNCs@MIPs) based on copper nanoclusters (CuNCs) and molecular imprinted polymers (MIPs) has been firstly reported. CuNCs was environment-friendly synthesized using poly(vinylpyrrolidone) as a template and ascorbic acid as a reducing agent. After functionalized with molecular imprinting technique, the CuNCs@MIPs probe has special binding cavities on surface to target etomidate, causing the fluorescence intensity rapidly decrease, which confirmed it has excellent sensitivity, selectivity and stability. Under optimal conditions, the fluorescent sensing probe presented high precision linear relationship for etomidate in range of 10-500 ng/ml with detection limit of 10 ng/ml, and the whole detection process was completed within 10 min. This sensing method has also been applied to real samples detection, still demonstrated excellent feasibility in electronic cigarette liquids and urine. More importantly, compared with previous methods, this fluorescent sensing method has advantages such as rapid, simple and easy to operate. Collectively, the proposed CuNCs@MIPs sensing probe has good fluorescence characteristics and simple synthesis strategy, showed a great potential in etomidate detection and application.
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  • 文章类型: Journal Article
    依托咪酯是一种全身麻醉药,具有良好的血流动力学稳定性,没有明显的心血管或呼吸抑制。尽管已经报道了这种药物的几种剂型,在临床实践中,制剂类型非常有限,这种中枢神经系统(CNS)药物的脑靶向制剂很少报道。此外,关于生物相容性的研究,毒性,依托咪酯制剂在体内的麻醉效果不足。本研究旨在开发乳铁蛋白修饰的脂质体依托咪酯(Eto-lip-LF),以增强药物在大脑中的分布并改善麻醉效果。Eto-lip-LF具有良好的储存稳定性和静脉注射血液相容性。与不含乳铁蛋白的脂质体相比,乳铁蛋白修饰的脂质体在体内脑靶向能力显著增强,这可能是通过转铁蛋白与大脑中高度分布的转铁蛋白和乳铁蛋白受体的结合来实现的。Eto-lip-LF的治疗指数约为25.3,高于许多其他全身麻醉药。此外,与市售依托咪酯乳剂相比,Eto-lip-LF能较好地实现全身麻醉的快速起效和麻醉的快速恢复,可能是由于增强了对大脑的药物输送。上述结果表明,这种乳铁蛋白修饰的脂质体依托咪酯有可能成为临床全身麻醉的替代制剂。
    Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations for this central nervous system (CNS) drug have been rarely reported. Moreover, studies on the biocompatibility, toxicity, and anesthetic effects of the etomidate preparations in vivo were inadequate. The present study was to develop lactoferrin-modified liposomal etomidate (Eto-lip-LF) for enhanced drug distribution in the brain and improved anesthetic effects. Eto-lip-LF had good stability for storage and hemocompatibility for intravenous injection. Compared with the non-lactoferrin-containing liposomes, the lactoferrin-modified liposomes had notably enhanced brain-targeting ability in vivo, which was probably realized by the binding of transferrin with the transferrin and lactoferrin receptors highly distributed in the brain. Eto-lip-LF had a therapeutic index of about 25.3, higher than that of many other general anesthetics. Moreover, compared with the commercial etomidate emulsion, Eto-lip-LF could better achieve rapid onset of general anesthesia and rapid recovery from anesthesia, probably due to the enhanced drug delivery to the brain. The above results demonstrated the potential of this lactoferrin-modified liposomal etomidate to become an alternative preparation for clinical general anesthesia.
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  • 文章类型: Case Reports
    低钾血症是一种常见的临床疾病,可导致肌肉无力,呼吸困难,恶性心律失常,甚至死亡。本报告描述了两例因使用含有依托咪酯的电子烟而导致的严重低钾血症,均伴有不同程度的肾上腺增生。在这两种情况下,患者因下肢无力和行走困难而入院。相关检查显示低血钾,皮质醇低,高促肾上腺皮质激素,低肾素,患者的醛固酮水平较低,病例2也有明显的高血压。在这两种情况下,肾上腺CT扫描显示肾上腺增厚。在两种情况下都补充钾之后,血钾水平逐渐恢复正常,肌肉力量逐渐改善。病例报告后,回顾了有关依托咪酯及其相关作用机制的文献,并讨论了其与低钾血症的相关性。
    Hypokalemia is a common clinical condition that can lead to muscle weakness, difficulty breathing, malignant arrhythmias, and even death. This report describes two cases of severe hypokalemia resulting from the use of electronic cigarettes containing etomidate, both accompanied by varying degrees of adrenal hyperplasia. In both cases, the patients were admitted to the hospital with lower limb weakness and difficulty walking. Relevant examinations revealed low blood potassium, low cortisol, high adrenocorticotropic hormone, low renin, and low aldosterone levels in the patients, with Case 2 also having significant hypertension. In both cases, adrenal CT scans showed thickening of the adrenal glands. After the delivery of potassium supplementation in both cases, blood potassium levels gradually returned to normal and muscle strength gradually improved. The case reports are followed by a review of the literature on etomidate and its related mechanisms of action with discussion of its association with hypokalemia.
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  • 文章类型: Journal Article
    背景:诱导后低血压(PIHO)是全身麻醉诱导过程中常见的血流动力学异常。依托咪酯被认为是麻醉诱导的更安全的药物,因为它对心血管和肺系统只有轻微的副作用。最近的证据表明,新型的苯并二氮杂列瑞米唑仑对循环和呼吸的抑制作用最小。然而,瑞咪唑安定与依托咪酯在麻醉诱导中的有效性和安全性尚不清楚.
    目的:为了进一步了解瑞马唑仑在麻醉诱导中的潜力,有必要设计一项荟萃分析,以比较其与经典安全麻醉剂依托咪酯的效果.这项研究的目的是确定哪种药物具有更稳定的血流动力学和更低的PIHO发生率。我们的研究还将产生镇静效率的数据,失去意识的时间,觉醒的时间,注射疼痛的发生率,和术后恶心呕吐两种药物。
    方法:我们计划搜索科学网,科克伦图书馆,Embase,PubMed,中国国家知识基础设施,和万方数据库自创建之日起至2025年3月31日。语言仅限于英语和汉语。搜索词是“随机对照试验,\"\"依托咪酯,\"和\"雷米唑仑。“PIHO的发病率是主要结果指标。次要结果包括诱导后的麻醉深度,镇静成功率,失去意识的时间,血液动力学曲线,恢复时间,注射疼痛的发生率,术后恶心呕吐。评论,荟萃分析,案例研究,会议摘要,和评论将不包括在内。结果的异质性将通过敏感性和亚组分析进行评估。将使用RevMan软件和Stata软件进行数据分析。我们将使用Cochrane偏见风险工具的第2版评估纳入研究的质量。将通过建议分级来评估证据的可信度,评估,事态发展,和评估系统。
    结果:该协议于2023年11月在国际PROSPERO(前瞻性系统审查登记册)注册表中注册。截至2024年6月,我们已经进行了初步的文章搜索和检索,以便进一步审查。审查和分析预计将于2025年3月完成。我们预计在2025年6月底之前提交手稿供同行评审。
    结论:通过综合现有证据并比较雷米咪唑安定和依托咪酯,我们希望为麻醉诱导药物的选择提供有价值的见解,以降低PIHO的发生率并改善患者预后.
    背景:PROSPEROCRD42023463120;https://tinyurl.com/333jb8bm.
    PRR1-10.2196/55948。
    BACKGROUND: Postinduction hypotension (PIHO) is a hemodynamic abnormality commonly observed during the induction of general anesthesia. Etomidate is considered a safer drug for the induction of anesthesia because it has only minor adverse effects on the cardiovascular and pulmonary systems. Recent evidence indicates that the novel benzodiazepine remimazolam has minimal inhibitory effects on the circulation and respiration. However, the efficacy and safety of remimazolam versus etomidate in the induction of anesthesia are unclear.
    OBJECTIVE: To further understand the potential of remimazolam in anesthesia induction, it is necessary to design a meta-analysis to compare its effects versus the classic safe anesthetic etomidate. The aim of this study is to determine which drug has more stable hemodynamics and a lower incidence of PIHO. Our study will also yield data on sedation efficiency, time to loss of consciousness, time to awakening, incidence of injection pain, and postoperative nausea and vomiting with the two drugs.
    METHODS: We plan to search the Web of Science, Cochrane Library, Embase, PubMed, China National Knowledge Infrastructure, and Wanfang databases from the date of their creation until March 31, 2025. The language is limited to English and Chinese. The search terms are \"randomized controlled trials,\" \"etomidate,\" and \"remimazolam.\" The incidence of PIHO is the primary outcome measure. Secondary outcomes include depth of anesthesia after induction, sedation success rate, time to loss of consciousness, hemodynamic profiles, recovery time, incidence of injection pain, and postoperative nausea and vomiting. Reviews, meta-analyses, case studies, abstracts from conferences, and commentaries will not be included. The heterogeneity of the results will be evaluated by sensitivity and subgroup analyses. RevMan software and Stata software will be used for data analysis. We will evaluate the quality of included studies using version 2 of the Cochrane risk-of-bias tool. The confidence of the evidence will be assessed through the Grading of Recommendations, Assessments, Developments, and Evaluations system.
    RESULTS: The protocol was registered in the international PROSPERO (Prospective Register of Systematic Reviews) registry in November 2023. As of June 2024, we have performed a preliminary article search and retrieval for further review. The review and analyses are expected to be completed in March 2025. We expect to submit manuscripts for peer review by the end of June 2025.
    CONCLUSIONS: By synthesizing the available evidence and comparing remimazolam and etomidate, we hope to provide valuable insights into the selection of anesthesia-inducing drugs to reduce the incidence of PIHO and improve patient prognosis.
    BACKGROUND: PROSPERO CRD42023463120; https://tinyurl.com/333jb8bm.
    UNASSIGNED: PRR1-10.2196/55948.
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  • 文章类型: Journal Article
    依托咪酯(ETO),一种用于麻醉诱导的催眠药,已被证明会导致长期的认知缺陷。在本研究中,我们研究了ETO是否可以激活HIF1A/PGK1通路来拮抗术后认知功能障碍(POCD)小鼠的氧化损伤.建立ETO介导POCD的小鼠模型,和病理变化,凋亡,HE染色分析小鼠海马组织炎症因子,TUNEL检测,和ELISA。ETO被发现会导致小鼠的认知功能障碍。进行综合数据库挖掘以筛选出与ETO和POCD均相关的转录因子。缺氧诱导因子1-α(HIF1A)在POCD小鼠中过度表达,HIF1A的下调减轻了小鼠的认知功能障碍。HIF1A下调抑制磷酸甘油酸激酶1(PGK1)的转录。PGK1的过表达减轻了HIF1A敲低对POCD小鼠氧化应激的缓解作用。此外,PGK1的HIF1A激活诱导HT-22细胞的氧化应激和凋亡,同时抑制细胞活力。一起来看,我们证明了PGK1的HIF1A激活在ETO介导的POCD中诱导氧化应激。
    Etomidate (ETO), a hypnotic agent used for anesthesia induction, has been shown to induce long-lasting cognitive deficits. In the present study, we investigated whether ETO could activate the HIF1A/PGK1 pathway to antagonize oxidative damage in mice with postoperative cognitive dysfunction (POCD). A mouse model of ETO-mediated POCD was established, and pathological changes, apoptosis, and inflammatory factors in mouse hippocampal tissues were analyzed by HE staining, TUNEL assay, and ELISA. ETO was revealed to cause cognitive dysfunction in mice. Integrated database mining was conducted to screen out transcription factors that are both related to ETO and POCD. Hypoxia-inducible factor 1-alpha (HIF1A) was overexpressed in mice with POCD, and downregulation of HIF1A alleviated cognitive dysfunction in mice. HIF1A downregulation inhibited the transcription of phosphoglycerate kinase 1 (PGK1). Overexpression of PGK1 abated the alleviating effects of HIF1A knockdown on oxidative stress in mice with POCD. In addition, HIF1A activation of PGK1 induced oxidative stress and apoptosis in HT-22 cells while inhibiting cell viability. Taken together, we demonstrated that HIF1A activation of PGK1 induced oxidative stress in ETO-mediated POCD.
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  • 文章类型: Journal Article
    依托咪酯(ET),一种用于麻醉诱导的催眠药,在肝脏中迅速代谢为依托咪酯酸(ETA)。最近,ET已成为中国滥用最严重的替代药物之一。因此,迫切需要开发一种快速方便的监测ET的分析方法。目前的工作提出了一个简单的,快,和灵敏的直接进样法测定废水中ET和ETA。经过超高效液相色谱-串联质谱和样品过滤条件的优化,该方法具有令人满意的检测限(1ng/L)和良好的过滤损失。经过验证的方法已成功用于测定中国几个污水处理厂废水样品(n=245)中ET和ETA的浓度。阳性样品中靶标的浓度范围从低于定量下限到47.71ng/L。该方法可以满足ET监测和高通量分析的要求。
    Etomidate (ET), a hypnotic agent used for the induction of anesthesia, is rapidly metabolized to etomidate acid (ETA) in the liver. Recently, ET has become one of the most serious alternative drugs of abuse in China. Therefore, an urgent need exists to develop a fast and convenient analysis method for monitoring ET. The current work presents a simple, fast, and sensitive direct injection method for the determination of ET and ETA in wastewater. After the optimization of the ultra-performance liquid chromatography-tandem mass spectrometry and sample filtration conditions, the method exhibited satisfactory limits of detection (1 ng/L) and good filtration loss. The validated method was successfully applied to determine the concentrations of ET and ETA in wastewater samples (n = 245) from several wastewater treatment plants in China. The concentrations of the targets in positive samples ranged from less than the lower limits of quantitation to 47.71 ng/L. The method can meet ET monitoring and high-throughput analysis requirements.
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  • 文章类型: Journal Article
    依托咪酯是源自咪唑的非巴比妥镇静剂。长期和过度使用依托咪酯可导致肾上腺皮质功能的抑制,肌阵鸣,甚至死亡。该报告描述了一例罕见的病例,一例47岁的男子因口服含依托咪酯的液体而死于急性中毒。根据全面调查,死因最终归因于依托咪酯,包括尸检,组织病理学检查,毒理学分析,和生化分析。这是首次报道的仅因口服依托咪酯引起的死亡病例,这可以为未来涉及依托咪酯中毒的法医调查提供有价值的见解。因此,必须与科学界分享这一案例。
    Etomidate is a nonbarbiturate sedative derived from imidazole. Prolonged and excessive use of etomidate can lead to the suppression of adrenocortical function, myoclonus, and even death. This report describes a rare case of a 47-year-old man who died from acute intoxication after oral ingestion of liquid containing etomidate. The cause of death was conclusively attributed to etomidate based on a comprehensive investigation, including autopsy, histopathological examination, toxicological analysis, and biochemical analysis. This is the first reported case of a fatality solely resulting from the oral ingestion of etomidate, which can provide valuable insights for future forensic investigations involving etomidate poisoning. Therefore, it is imperative to share this case with the scientific community.
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  • 文章类型: Journal Article
    依托咪酯(ETO)在手术中用作麻醉剂,但它在某些人群中被滥用。长期摄入ETO对肠道和大脑功能的损害尚不清楚,该药物是否通过肠-脑轴影响中枢神经系统仍有待确定。本研究旨在研究ETO在1mg/kg和3mg/kg剂量下连续14天对小鼠的神经毒性和胃肠道作用。结果表明,长期注射ETO导致小鼠耐药,影响他们对黑暗的天生偏好,并可能诱导对ETO的依赖。大脑中5-羟色胺的水平,血清,结肠减少了37%,51%,分别为42%,而γ-氨基丁酸的水平降低了38%,52%,分别为41%。H&E染色显示ETO减少结肠中的杯状细胞并破坏肠屏障。紧密连接相关基因Claudin4和ZO-1的表达下调。肠道菌群发生了变化,Akkermansia和乳酸杆菌的丰度分别下降了33%和14%,分别,而克雷伯菌则增加了18%。TUNEL结果显示高剂量ETO增加脑中的凋亡细胞。大脑中Claudin1的表达下调。结肠和大脑的非靶向代谢组学分析表明,ETO引起甘油磷脂代谢异常。脂质代谢异常可能导致脂毒性代谢物的产生或积累,引起中枢神经系统疾病。ETO诱导肠道菌群和代谢的变化,通过肠脑轴进一步影响中枢神经系统。该研究揭示了长期摄入ETO对大脑和胃肠道系统的有害影响,这对理解滥用ETO对人类健康的不利影响具有重大影响。
    Etomidate (ETO) is used as an anesthetic in surgery, but it is being abused in some populations. The damage caused by long-term intake of ETO to intestinal and brain functions is not yet clear, and it remains to be determined whether the drug affects the central nervous system through the gut-brain axis. This study aimed to investigate the neurotoxic and gastrointestinal effects of ETO at doses of 1 mg/kg and 3 mg/kg in mice over 14 consecutive days. The results showed that long-term injection of ETO led to drug resistance in mice, affecting their innate preference for darkness and possibly inducing dependence on ETO. The levels of 5-hydroxytryptamine in the brain, serum, and colon decreased by 37%, 51%, and 42% respectively, while the levels of γ-aminobutyric acid reduced by 38%, 52%, and 41% respectively. H&E staining revealed that ETO reduced goblet cells in the colon and damaged the intestinal barrier. The expression of tight junction-related genes Claudin4 and ZO-1 was downregulated. The intestinal flora changed, the abundance of Akkermansia and Lactobacillus decreased by 33% and 14%, respectively, while Klebsiella increased by 18%. TUNEL results showed that high-dose ETO increased apoptotic cells in the brain. The expression of Claudin1 in the brain was downregulated. Untargeted metabolomics analysis of the colon and brain indicated that ETO caused abnormalities in glycerophospholipid metabolism. Abnormal lipid metabolism might lead to the production or accumulation of lipotoxic metabolites, causing central nervous system diseases. ETO induced changes in the intestinal flora and metabolism, further affecting the central nervous system through the gut-brain axis. The study unveiled the detrimental effects on the brain and gastrointestinal system resulting from long-term intake of ETO, which holds significant implications for comprehending the adverse impact of ETO abuse on human health.
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