Experimental and Therapeutic Medicine
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2017
·Vol. 14
·期 5
·4307-4311
·
IF 1.261
Tao Zhou,Shanliang Guo,Shaolin Wang,Qiong Li,Mingsheng Zhang
This study was designed to investigate possible protective effects of sevoflurane on myocardial ischemia-reperfusion injury (MIRI) and its impact on expression of HIF-1α and caspase-3 in rats, so as to provide new insights for the treatment of MIRI. Forty SD rats were randomly divided into four groups (n=10) including Sham operation (Sham), ischemia-reperfusion (IR), sevoflurane preconditioning group (Sevo-Pre) and sevoflurane post-conditioning (Sevo-Post) groups. Perfusion was performed using ex vivo heart perfusion. The baseline values of cardiac function were recorded in each group at the end of balanced perfusion and after 60 min of reperfusion. Myocardial infarct size (MIS) was calculated at the end of perfusion using TTC staining. Levels of HIF-1α and caspase-3 protein and HIF-1α (western blotting) and Bcl-2 mRNA (RT-qPCR) were detected at the end of reperfusion. Our results showed no significant differences in cardiac function between the groups at the end of the balanced perfusion. After reperfusion for 60 min, however, the cardiac functions of the Sevo-Pre and Sevo-Post groups were significantly better than those in the IR group, and the MIS at the end of reperfusion was significantly decreased. Western blotting and RT-qPCR showed that expression of HIF-1α protein was significantly increased, expression of caspase-3 protein was significantly decreased and expression of HIF-1α and Bcl-2 mRNA were significantly increased in Sevo-Pre and Sevo‑Post groups compared with the levels in the IR group at the end of reperfusion. There were no significant differences in experimental results between Sevo-Pre and Sevo-Post groups. Our data support the idea that sevoflurane can improve MIRI in rats by improving cardiac function and reducing MIS. This protective effect seems to be achieved by activation of HIF-1α and inhibition of caspase-3.
研究领域:
药理学
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心脏病学
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分子生物学
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DOI
PubMed
高影响因子
CHINESE MEDICAL JOURNAL
·
2025
·
IF 7.3
Jia Pengyu,Wang Kui,Cheng Yiqin,Zhang Yan,Lu Yuying,Sun Haodong,Zhang Shuyue,Fan Pei,Zhang Yuanyuan,Yang Liufei,Wang Ning,Lu Haixia,Chen Xinlin,Liu Yong,Wei Haidong,Zhang Pengbo
Plain Language Summary Background: Sevoflurane impairs neurogenesis and cognitive function in the developing brain; however, the underlying mechanisms remain unclear. This study aimed to investigate the role of fatty acid β-oxidation (FAO) in neural stem/progenitor cells (NSPCs) as a potential factor in sevoflurane-induced neurogenesis inhibition and cognitive deficits. Methods: NSPCs, NE-4C cells, and postnatal day 7 (PND 7) rats were exposed to sevoflurane. Cell viability was measured using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Neurogenesis was assessed by immunohistochemistry. Apoptosis was detected via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Cognitive function was tested with the Morris water maze. Lipid metabolism profiles were analyzed through lipidomics. Message RNA (mRNA) expression levels of key FAO enzymes and the major carnitine transporter were quantified by real-time reverse transcription polymerase chain reaction (RT-qPCR). Protein expression of carnitine palmitoyltransferase 1a (CPT1a) and nuclear peroxisome proliferator-activated receptor α (PPARα) was examined by Western blotting. CPT1a enzymatic activity was determined using a biochemical assay. FAO activity was measured with the FAOBlue assay. Results: Sevoflurane exposure impaired neurogenesis and cognitive function. In NSPCs, sevoflurane exposure induced extensive alterations in lipid metabolism intermediates, inhibited the mRNA expression of acyl-CoA oxidase 1 ( ACOX1 ), acyl-CoA oxidase 3 ( ACOX3 ), hydroxyacyl-CoA dehydrogenase beta subunit ( HADHB ), CPT1a , carnitine palmitoyltransferase 2 ( CPT2 ), acyl-CoA dehydrogenase short-chain ( ACADS ), and solute carrier family 22 member 5 ( SLC22A5 ), suppressed FAO activity, reduced CPT1a expression and activity, and decreased PPARα levels in the nucleus. Enhancing FAO activity in NSPCs ameliorated the negative effects of sevoflurane on neurogenesis. Overexpression of CPT1a rescued the sevoflurane-induced inhibition of FAO activity and neurogenesis in NE-4C cells. Pretreatment with palmitoylethanolamide (PEA), a PPAPα agonist, increased both the nuclear content of PPARα protein and the expression of CPT1a in NSPCs and rat hippocampus after sevoflurane exposure. Furthermore, pretreatment with PEA or the CPT1a substrate carnitine rescued sevoflurane-induced damage to FAO activity in NSPCs, neurogenesis, and cognitive function. Conclusion: Sevoflurane impairs neurogenesis and cognitive function by suppressing FAO in NSPCs of the developing brain. Boosting FAO activity in NSPCs could be a potential strategy to prevent sevoflurane-induced cognitive deficits. Plain Language Summary This study explored how sevoflurane, an anesthetic, affects brain development by impairing neurogenesis and cognitive function. Researchers found that sevoflurane disrupts fatty acid β-oxidation (FAO) in neural stem/progenitor cells (NSPCs), leading to changes in lipid metabolism and reduced expression of key enzymes. Enhancing FAO activity, either by overexpressing certain proteins or using compounds like palmitoylethanolamide (PEA) and carnitine, helped mitigate these negative effects. This suggests that targeting FAO in NSPCs could be a promising approach to counteract sevoflurane-induced cognitive deficits in the developing brain. Text is machine generated and may contain inaccuracies. FAQ
研究领域:
神经科学
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发育生物学
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麻醉学
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代谢学
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干细胞研究
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DOI
高影响因子
American Journal of Translational Research
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2021
·
IF 4.06
Shan Jiang,Chonghe Wang,Jingyao Zhu,Xuezhu Huang
Objective: To investigate the regulatory mechanism of sevoflurane-induced neuronal apoptosis through analyzing the expression of glial cell-derived neurotrophic factor (GDNF) mediated by miR-133, sponged by long non-coding RNA (lncRNA) CDKN2B-AS1. Methods: An in vitro cell injury model was established by using different concentrations of sevoflurane and primary hippocampal neurons. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8); caspase-3 and caspase-9 activities were detected by colorimetry, and apoptotic cells were determined by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Fluorescence in situ hybridization (FISH) analysis was used to detect localized expression of CDKN2B antisense RNA 1 (CDKN2B-AS1), and dual-luciferase reporter assay was employed to verify the correlation of CDKN2B-AS1 and miR-133, and of miR-133 and GDNF. The expression of CDKN2B-AS1, miR-133, and GDNF mRNA in the cell injury model were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot was utilized to detect the expression of GDNF protein in the cell injury model. Results: In the cell injury model, CDKN2B-AS1 was highly expressed in the cytoplasm, and CDKN2B-AS1 and GDNF were downregulated and miR-133 was upregulated as detected by qRT-PCR (all P<0.05). The connections between CDKN2B-AS1 and miR-133, and between miR-133 and GDNF were confirmed. That is, CDKN2B-AS1 regulated the expression of GDNF by adsorbing miR-133 (all P<0.05). In cells treated with sevoflurane, overexpression of CDKN2B-AS1 could inhibit caspase-3 and caspase-9 activities and the degree of apoptosis. miR-133 could partially alleviate the effect of overexpressing CDKN2B-AS1 on cells, and si-GDNF the effect of miR-133 inhibitor (all P<0.05). Conclusion: lncRNA CDKN2B-AS1 can up-regulate the expression of GDNF, inhibit neuronal apoptosis, and ease the toxic effect of sevoflurane on neural cells by acting as a sponge to adsorb miR-133.
研究领域:
神经科学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
COPD-Journal of Chronic Obstructive Pulmonary Disease
·
2023
·
IF 2.2
Chuanxin Yang,Libing Deng,Fang Bao,Hui Jiang,Long Zhang
Chronic obstructive pulmonary disease (COPD) is a difficult-to-cure disease that mainly affects the respiratory system. Inhaled anesthetic drug such as sevoflurane plays a controversial role in COPD by different concentration, but the underlying epigenetic mechanism remains unclear. Here, we prepared lipopolysaccharide (LPS)-induced COPD rat model, and isolated Alveolar type II (ATII) cells. We mainly focused DNA methylation on the promoter of COPD-related genes including Sftpa1, Napsa, Ca2, Sfta2, Lamp3, Wif1, Pgc, and Etv5. We observed COPD rat treated by sevoflurane with low (0.5%) and high (2%) concentrations displayed an opposite DNA methylation pattern. These six genes' promoter were all hypomethylated by 0.5% sevoflurane whereas hypermethylated by 2% sevoflurane, accompanied with the opposite transcriptional activity. We further verified that the DNMT1 binding ability contributed to DNA methylation these six genes' promoter. Moreover, we also captured DNMT1 and identified REC8 meiotic recombination protein (REC8) as the specific binding protein only existed in ATII cells treated with 0.5% sevoflurane rather than 2% and control. The binding ability of REC8 on these target genes' promoter showed highly positive correlation with DNMT1. In summary, we uncovered a potential epigenetic role of sevoflurane with low concentration in ATII cells of COPD that may help us deeply understand the pathogenesis and treatment mechanism of inhaled anesthesia drugs in COPD via a dose-dependent manner.
研究领域:
肺病学
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分子生物学
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表观遗传学
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药理学
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DOI
高影响因子
ACS Chemical Neuroscience
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2024
·
IF 4.1
Wei Du,Xiaomin Zhang,Songze Li,Xin Xie
This study aims to investigate the role of neuronal SIRPα and microglial synaptic remodeling in sevoflurane-induced cognitive dysfunction in newborn mice. Newborn mice were exposed to sevoflurane, followed by behavioral assessments and single-cell transcriptome sequencing of cortical cells. Lentivirus-mediated overexpression of neuronal SIRPα and assessment of the microglial morphology and synaptic function were conducted. Sevoflurane exposure resulted in social cognitive impairments without affecting motor coordination. Transcriptomic analysis revealed no significant changes in cortical microglial cells or neurons. However, sevoflurane inhibited nonsynaptic synapse modification by microglia. Overexpression of neuronal SIRPα enhanced microglial function, promoted neuron development, and ameliorated cognitive impairments. SCENIC analysis identified a correlation between IRF8 and SIRPα expression. This study sheds light on the involvement of neuronal SIRPα and microglial synaptic remodeling in sevoflurane-induced cognitive dysfunction. Understanding these mechanisms offers new avenues for exploring cognitive impairment pathways and potential therapeutic targets.
研究领域:
神经科学
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分子生物学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
NEUROCHEMISTRY INTERNATIONAL
·
2021
·
IF 3.921
Ying Xu,Yunxia Dong,Cong Wang,Qian Jiang,Haichao Chu,Yue Tian
As a general anesthetic widely used in surgical, sevoflurane has been shown to cause cognitive and memory deficits in the elderly. It's important to find out agents that can counteract sevoflurane-induced cognitive dysfunction. This study is aimed to investigate the effect of lovastatin on sevoflurane-induced cognitive impairment in aged rats and reveal the potential mechanisms. BV-2 cells, rat hippocampal neurons or male aged rats were exposed to 2% sevoflurane for 5 h. The cells were pretreated with 10 μM lovastatin. The rats were intraperitoneally injected with 5 mg/kg/day lovastatin for three days. The results showed that lovastatin enhanced exosomal IDE secretion from sevoflurane-exposed BV-2 cells and promoted Aβ degradation. Lovastatin treatment also inhibited the increased expressions of β-secretase 1 (BACE1) and γ-secretase in hippocampal neurons under sevoflurane exposure in vitro . In animal experiments, the discrimination index in novel object recognition test and percentage of spontaneous alternation in Y-maze test were significantly elevated after lovastatin administration. In addition, Aβ plaque area and contents of soluble Aβ 1-40 and Aβ 1-42 in the hippocampal tissues were decreased upon lovastatin treatment. Furthermore, lovastatin reversed sevoflurane-induced Aβ accumulation via up-regulating IDE expression, and down-regulating amyloid precursor protein (APP)-related protein expression (β-C-terminal fragment (CTF), BACE1 and γ-secretase). In conclusion, lovastatin alleviates sevoflurane-induced cognitive deficient in aged rats via promoting Aβ degradation and reducing Aβ production. Lovastatin may be beneficial in preventing anesthetic-induced cognitive impairment.
研究领域:
神经科学
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药理学
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麻醉学
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老年医学
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产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
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2024
·
IF 4.2
Tingting Wang,Xia Wu,Xiaoli Zhao,Jiaqi Li,Jian Yu,Maozheng Sheng,Mingyuan Gao,Yutang Cao,Jiawen Wang,Xiaozhen Guo,Kai Zeng
Purpose Postoperative cognitive dysfunction (POCD) is a central nervous system complication that occurs after anesthesia, particularly among the elderly. However, the neurological pathogenesis of postoperative cognitive dysfunction remains unclear. The aim of this study was to evaluate the effects of sevoflurane exposure on serum metabolites and hippocampal gene expression in elderly patients and aging mice by metabolomics and transcriptomic analysis and to explore the pathogenesis of sevoflurane induced POCD.Patients and Methods Human serum samples from five patients over 60 years old were collected before sevoflurane anesthesia and 1 hour after anesthesia. Besides, mice aged at 12 months (n=6 per group) were anesthetized with sevoflurane for 2 hours or with sham procedure. Subsequently, serum and hippocampal tissues were harvested for analysis. Further investigation into the relationship between isatin and neuroinflammation was conducted using BV2 microglial cells.Results Sevoflurane anesthesia led to the activation of inflammatory pathways, an increased presence of hippocampal astrocytes and microglia, and elevated expression of neuroinflammatory cytokines. Comparative analysis identified 12 differential metabolites that exhibited changes in both human and mouse serum post-sevoflurane anesthesia. Notably, isatin levels were significantly decreased after anesthesia. Notably, isatin levels significantly decreased after anesthesia, a factor known to stimulate proliferation and proinflammatory gene expression in microglia—the pivotal cell type in inflammatory responses.Conclusion Sevoflurane-induced alterations in serum metabolites in both elderly patients and aging mice, subsequently contributing to increased inflammation in the hippocampus.
研究领域:
麻醉学
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神经科学
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老年医学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2024
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IF 4.2
Xiaochun Zhao,Xueting Wang,Ziyang Xu,Xiaohan Chang,Yue Tian
Perioperative neurocognitive disorders (PNDs) are common neurological complications after anesthesia in the elderly. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) regulates signal transducer and activator of transcription protein 3 (STAT3) signaling to control inflammation in certain organs, but its role in PNDs remains unknown. Herein, we constructed a PND model in 18-month-old rats by treating them with sevoflurane. PND rats developed neuroinflammation, along with a significant decrease in PTPN2 expression and a rise in STAT3 phosphorylation in the hippocampus. Ptpn2 overexpression alleviated the behavioral disorders of PND rats, ameliorated neuronal injury, inhibited neuroinflammation, inflammasome activation, microglial activation, and microglial phenotype switching. Similar results were observed in sevoflurane-treated HMC3 microglia with PTPN2 overexpression, while PTPN2 silencing showed the opposite results. Additionally, PTPN2 seems to be a target of T-box transcription factor 2 (TBX2). These results contribute to the evidence supporting the idea that PTPN2 is a regulatory factor in PND progression.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
ACTA HISTOCHEMICA
·
2019
·
IF 1.719
Yang Wang,Chun Wang,Yue Zhang,Guan Wang,Haitao Yang
Sevoflurane is a widely used inhaled anesthetic , which triggers neuroapoptosis and oxidative damage in the developing central nervous system and cognitive dysfunction later in life. However, no effective therapeutic strategy for sevoflurane-induced deleterious effects is well developed. The purpose of the present study was to explore whether luteoline could attenuate neonatal sevoflurane exposure-triggered neurotoxicity . In this study, six-day-old C57BL/6 mice were pretreated with luteoline (30, 60 mg/kg) intraperitoneally for 30 min before exposed to 3% sevoflurane 6 h consecutively. We first examined the effects of luteoline on hippocampal neuron apoptosis, inflammation and oxidative stress 18 h post anesthesia. The spatial learning and memory performance was measured using Morris water maze test from postnatal day 31 to 38. The results showed that luteoline ameliorated neuronal apoptosis as evidenced by decrease of apoptotic cells, downregulation of the cleavage levels of caspase-3 and PRAP, and inactivation of caspase-3. Moreover, luteoline significantly decreased protein expressions of inflammatory cytokines (IL-1β, IL-18 and TNF-α), inhibited NF-кB/NLRP3 pathway (NF-кB, NLRP3 , ASC and caspase-1) and suppressed NF-кB activity. Our analyses indicated that luteoline had a significant effect on decreasing the contents of ROS and MDA , elevating the activity of SOD, and ultimately improving spatial learning and memory deficits of mice. In summary, our findings confirm that the attenuation of luteoline on sevoflurane-induced spatial learning and memory impairment later is associated with inhibition of hippocampal neuron apoptosis, inflammation and oxidative stress early. Luteoline might be a potential therapeutic for sevoflurane anesthesia-induced neurobehavioral dysfunction.
研究领域:
药理学
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神经科学
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麻醉学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2023
·Vol. 26
·期 1
·1-10
·
IF 2.7
Ying Deng,Jing-Shu Hong,Yi-Yun Cao,Ning Kang,Deng-Yang Han,Yi-Tong Li,Lei Chen,Zheng-Qian Li,Rui Zhan,Xiang-Yang Guo,Ning Yang,Cheng-Mei Shi
Postoperative delirium (POD), which occurs in hospital up to 1‑week post‑procedure or until discharge, is a common complication, especially in older adult patients. However, the pathogenesis of POD remains unclear. Although damage to blood‑brain barrier (BBB) integrity is involved in the neuropathogenesis of POD, the specific role of the BBB in POD requires further elucidation. Anaesthesia using 2% isoflurane for 4 h results in the upregulation of hippocampal receptor for advanced glycation end‑products (RAGE) expression and β‑amyloid accumulation in aged rats. The present study investigated the role of RAGE in BBB integrity and its mechanisms in POD‑like behaviours. The buried food, open field and Y maze tests were used to evaluate neurobehavioural changes in aged mice following 2.5% sevoflurane anaesthesia administration with exploratory laparotomy. Levels of tight junction proteins were assessed by western blotting. Multiphoton in vivo microscopy was used to observe the ultrastructural changes in the BBB in the hippocampal CA1 region. Anaesthesia with surgery decreased the levels of tight junction proteins occludin and claudin 5, increased matrix metalloproteinases (MMPs) 2 and 9, damaged the ultrastructure of the BBB and induced POD‑like behaviour. FPS‑ZM1, a specific RAGE antagonist, ameliorated POD‑like behaviour induced by anaesthesia and surgery in aged mice. Furthermore, FPS‑ZM1 also restored decreased levels of occludin and claudin 5 as well as increased levels of MMP2 and MMP9. The present findings suggested that RAGE signalling was involved in BBB damage following anaesthesia with surgery. Thus, RAGE has potential as a novel therapeutic intervention for the prevention of POD.
研究领域:
神经科学
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麻醉学
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老年医学
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药理学
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产品关联
DOI
高影响因子
BRAIN RESEARCH BULLETIN
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2021
·
IF 4.079
Hongzhi Chen,Haichao Chu,Qian Jiang,Cong Wang,Yue Tian
Perioperative neurocognitive disorder (PND) frequently occurs in elderly patients following anesthesia, and is associated with pro-inflammatory activation of microglia in hippocampus. In this study, sevoflurane , a commonly used inhaled anesthetic in clinic, was used to induce PND-like symptoms in aged SD rats (18–20 months). Data from novel object recognition and Y-maze tests first confirmed that aged SD rats exposed to 2% sevoflurane for 5 h developed cognitive impairment . Microglia preferred to polarizing towards pro-inflammatory M1 subtype (iNOS+Iba-1 +) in rat hippocampus post sevoflurane exposure, but not anti-inflammatory M2 subtype (Arg-1 +Iba-1 +). Microarray data identified interferon regulatory factor 6 (Irf6) as one (Fold change = −2.52, p = 0.006) of the 15 downregulated genes in hippocampus of the rats exposed to sevoflurane. Co-immunofluorescence data further illustrated that sevoflurane decreased Irf6 expression in hippocampal microglia. In vitro, sevoflurane enhanced lipopolysaccharide-induced M1 polarization of BV-2 cells and inhibited interleukin-4 induced M2 polarization. Interestingly, manipulation of Irf6 expression hardly affected M1 polarization. However, Irf6 overexpression further augmented the inhibitory effects on M2 polarization, and its silencing showed opposite effects. In addition, such M2 polarization-promoting effects of Irf6 knockdown may be associated with induction of peroxisome proliferator activated receptor gamma expression. Collectively, these findings suggest that Irf6 downregulation in hippocampal microglia may be a compensatory mechanism against sevoflurane-induced PND in the elderly.
研究领域:
神经科学
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麻醉学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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