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N-methyl-D-aspartate receptor subtype 3A promotes apoptosis in developing mouse brain exposed to hyperoxia
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作者 Jimei Li Shanping Yu +2 位作者 Zhongyang Lu Osama Mohamad Ling Wei 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第4期273-277,共5页
In the present study, 7 day postnatal C57/BL6 wild-type mice (hyperoxia group) and 7 day postnatal N-methyI-D-aspartate receptor subtype 3A knockout mice (NR3A KO group) were exposed to 75% oxygen and 15% nitrogen... In the present study, 7 day postnatal C57/BL6 wild-type mice (hyperoxia group) and 7 day postnatal N-methyI-D-aspartate receptor subtype 3A knockout mice (NR3A KO group) were exposed to 75% oxygen and 15% nitrogen in a closed container for 5 days. Wild-type mice raised in normoxia served as controls. TdT-mediated dUTP nick end labeling (TUNEL)/neuron-specific nuclear protein (NeuN) and 5-bromo-2'-deoxyuridine (BrdU)/NeuN immunofluorescence staining showed that the number of apoptotic cells and the number of proliferative cells in the dentate subgranular zone significantly increased in the hyperoxia group compared with the control group. However, in the same hyperoxia environment, the number of apoptotic cells and the number of proliferative cells significantly decreased in the NR3A KO group compared with hyperoxia group. TUNEL+/NeuN+ and BrdU+/NeuN~ cells were observed in the NR3A KO and the hyperoxia groups. These results demonstrated that the NR3A gene can promote cell apoptosis and mediate the potential damage in the developing brain induced by exposure to non-physiologically high concentrations of oxygen. 展开更多
关键词 n-methyl-d-aspartate receptor subtype 3a apoptosis cell proliferation HYPEROXIA developing brain nerve cells MOUSE NEUROBIOLOGY neural regeneration
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Gamma-aminobutyric acid promotes human hepatocellular carcinoma growth through overexpressed gamma-aminobutyric acid A receptor α3 subunit 被引量:9
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作者 Yan Liu Yue-Hui Li Feng-Jie Guo Jia-Jia Wang Rui-Li Sun Jin-Yue Hu Guan-Cheng Li 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第47期7175-7182,共8页
AIM:To investigate the expression pattern of gamma-aminobutyric acid A(GABAA) receptors in hepatocellular carcinoma(HCC) and indicate the relationship among gamma-aminobutyric acid(GABA),gamma-aminobutyric acid A rece... AIM:To investigate the expression pattern of gamma-aminobutyric acid A(GABAA) receptors in hepatocellular carcinoma(HCC) and indicate the relationship among gamma-aminobutyric acid(GABA),gamma-aminobutyric acid A receptor α3 subunit(GABRA3) and HCC.METHODS:HCC cell line Chang,HepG2,normal liver cell line L-02 and 8 samples of HCC tissues and paired non-cancerous tissues were analyzed with semiquantitative polymerase chain reaction(PCR) for the expression of GABAA receptors.HepG2 cells were treated with gamma-aminobutyric acid(GABA) at serial concentrations(0,1,10,20,40 and 60 μmol/L),and their proliferating abilities were analyzed with the 3-(4,5-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay,cell doubling time test,colon formation assay,cell cycle analysis and tumor planted in nude mice.Small interfering RNA was used for knocking down the endogenous GABRA3 in HepG2.Proliferating abilities of these cells treated with or without GABA were analyzed.RESULTS:We identified the overexpression of GABRA3 in HCC cells.Knockdown of endogenous GABRA3 expression in HepG2 attenuated HCC cell growth,suggesting its role in HCC cell viability.We determined the in vitro and in vivo effect of GABA in the proliferation of GABRA3-positive cell lines,and found that GABA increased HCC growth in a dose-dependent manner.Notably,the addition of GABA into the cell culture medium promoted the proliferation of GABRA3-expressing HepG2 cells,but not GABRA3-knockdown HepG2 cells.This means that GABA stimulates HepG2 cell growth through GABRA3.CONCLUSION:GABA and GABRA3 play important roles in HCC development and progression and can be a promising molecular target for the development of new diagnostic and therapeutic strategies for HCC. 展开更多
关键词 Hepatocellular carcinoma PROLIFERATION Gamma-aminobutyric acid Gamma-aminobutyric acid A receptor a3 subunit RNAI
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Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome:A multicenter retrospective study 被引量:3
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作者 Sabrina Berens Yuanjun Dong +30 位作者 Nikola Fritz Jutta Walstab Mauro D'Amato Tenghao Zheng Verena Wahl Felix Boekstegers Justo Lorenzo Bermejo Cristina Martinez Stefanie Schmitteckert Egbert Clevers Felicitas Engel Annika Gauss Wolfgang Herzog Robin Spiller Miriam Goebel-Stengel Hubert Mönnikes Viola Andresen Frieling Thomas Jutta Keller Christian Pehl Christoph Stein-Thöringer Gerard Clarke Timothy G Dinan Eamonn M Quigley Gregory Sayuk Magnus Simrén Jonas Tesarz Gudrun Rappold Lukas van Oudenhove Rainer Schaefert Beate Niesler 《World Journal of Gastroenterology》 SCIE CAS 2022年第21期2334-2349,共16页
BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bo... BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS. 展开更多
关键词 Irritable bowel syndrome 5-HT3 receptor subunit gene polymorphisms Single-nucleotide polymorphism score Depression ANXIETY SOMATIZATION
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Role of α3 nicotinic acetylcholine receptor subunit in the inflammatory responses of atherosclerosis
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《中国药理学通报》 CAS CSCD 北大核心 2015年第B11期187-187,共1页
Aim The expression of α3 subunit of nicotinic acetylcholine receptor (α3-nAChR) has been demonstra- ted in aorta, adipocyte and macrophage. The objective of the present study was to verify the regulatory roles of ... Aim The expression of α3 subunit of nicotinic acetylcholine receptor (α3-nAChR) has been demonstra- ted in aorta, adipocyte and macrophage. The objective of the present study was to verify the regulatory roles of α3- nAChR in the inflammatory responses of atherosclerosis. Methods The inflammatory indicators were detected in mouse macrophage, adipocytes and mouse aortic endothelial cells (MAECs) after the α3-nAChR was antagonized or after the α3-nAChR gene was silenced. Meanwhile, atherogenesis was induced in the apolipoprotein E knock-out ( ApoE^ -/- ) mice after fed with an atherogenic high-fat diet for 7 weeks. Results In MAECs, the lipopolysaccha- ride (LPS)-stimulated secretions of the adhesion molecules and inflammatory cytokines were significantly enhanced (30%± 80% ) after pretreatment with α-Conotoxin MII (an antagonist for α3-nAChR) or after knock-down with α3-nAChR gene. In adipocytes, the knock-down of α3 gene promoted the generations of the proin? ammatory adi- pokines or cytokines but decreased the production of adiponectin, an anti-inflammatory adipokine, by 29.29 ± 9.43%. In macrophage silenced with α3-nAChR gene, the M1 (classical) activation was predominantly stimula- ted, whereas the M2 (alternative) activation was suppressed. In addition, the amount of the atherosclerotic lesions and the infiltration of the M1 type activated macrophages into the arterial wall were markedly elevated in the α- Conotoxin MII-treated ApoE -/- mice. Conclusion The α3-nAChR may play a pivotal role in regulating the atherogenesis through influencing the inflammatory responses of ECs, macrophages and adipocytes. The mecha- nisms involve the regulations of multiple cell signaling pathways. 展开更多
关键词 NICOTINIC receptor subunit alpha3 ATHEROSCLEROSIS inflammation ENDOTHELIAL cell MACROPHAGE adi-pocyte
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Attenuation of nicotine-evoked Ca<sup>2+</sup>influx by antibody to the nicotinic acetylcholine receptor <i>α</i>3 subunits in human embryonic kidney cells
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作者 Shota Kobayashi Shigeru Yokoyama +3 位作者 Takahiro Maruta Akiko Muroyama Hiroaki Yoshikawa Yasuhide Mitsumoto 《Advances in Bioscience and Biotechnology》 2013年第6期9-14,共6页
Autoantibody against neuronal nicotinic acetylcholine receptor (nAChR) α3 subunit is implicated in severe autonomic dysfunction in the patients with autoimmune autonomic ganglionopathy (AAG). Although this autoantibo... Autoantibody against neuronal nicotinic acetylcholine receptor (nAChR) α3 subunit is implicated in severe autonomic dysfunction in the patients with autoimmune autonomic ganglionopathy (AAG). Although this autoantibody has been revealed to impair fast excitatory synaptic transmission in autonomic ganglia, its precise mechanism remains unknown. Here, we show that antibody-induced reduction of cell-surface α3 subunits result in impairment of nicotine-evoked Ca2+ influx in stably transfected human embryonic kidney cells. These effects of the antibody were remarkably inhibited by interfering with the endocytic machinery at low-temperature. We conclude that reduction of nAChR in autonomic ganglia can be mediated by the endocytosis of α3 subunits, and resulted in autonomic failure in AAG patients. 展开更多
关键词 NICOTINIC Acetylcholine receptor α3 subunit ANTIBODY Endocytosis Ca2+ INFLUX Autoimmune Autonomic Ganglionopathy
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Gabra3通过AKT/mTOR途径促进膀胱癌T24细胞侵袭和迁移
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作者 李明明 韩利忠 +2 位作者 王亚楠 卢冠军 吕志勇 《现代肿瘤医学》 CAS 2024年第7期1208-1214,共7页
目的:探究γ-氨基丁酸受体亚基α-3(Gamma-aminobutyric acid receptor subunit alpha-3,Gabra3)基因对膀胱癌T24细胞凋亡、迁移和侵袭的作用及其机制。方法:TCGA数据库分析Gabra3基因在膀胱癌中的表达以及转移和生存的相关性。建立Gab... 目的:探究γ-氨基丁酸受体亚基α-3(Gamma-aminobutyric acid receptor subunit alpha-3,Gabra3)基因对膀胱癌T24细胞凋亡、迁移和侵袭的作用及其机制。方法:TCGA数据库分析Gabra3基因在膀胱癌中的表达以及转移和生存的相关性。建立Gabra3过表达和Gabra3突变的T24细胞株,根据转染质粒不同,分为空白T24细胞(Control)、空pDONR223载体转染T24细胞(NC)、野生型Gabra3过表达T24细胞株(wt-Gabra3)、突变型Gabra3 T24细胞株(mut-Gabra3)。在回补实验中,分为转染突变型Gabra3 T24组(mut-Gabra3)、转染空pDONR223载体mut-Gabra3组(mut-Gabra3-NC)、转染野生型Gabra3过表达组(mut-Gabra3+wt-Gabra3)。用TUNEL染色检测T24细胞凋亡,细胞划痕和Transwell分别检测T24细胞迁移和侵袭,Western blot检测AKT/mTOR通路相关分子生物表达水平。结果:Gabra3基因在膀胱癌中显著高表达(P<0.05),生存曲线证实远处转移存在的患者生存期明显较短(P<0.05)。成功构建Gabra3过表达和突变的T24细胞株。与Control组相比,wt-Gabra3组细胞凋亡能力显著降低,迁移、侵袭能力显著增强(P<0.05),而mut-Gabra3组细胞凋亡显著增加,侵袭能力显著减弱(P<0.05);wt-Gabra3组细胞p-AKT、p-mTOR、p-4E-BP1、p-S6K蛋白表达均显示上凋(P<0.05),而mut-Gabra3组细胞上述蛋白无差异。在回补实验中,过表达wt-Gabra3的mut-Gabra3突变T24细胞凋亡能力受到抑制(P<0.05),迁移和侵袭能力显著增强(P<0.05),并且该组细胞AKT/mTOR通路相关分子显著激活(P<0.05)。结论:外源性的未编辑的Gabra3可以促进膀胱癌T24细胞的迁移、侵袭能力,并且可能与激活AKT/mTOR途径通路密切相关。 展开更多
关键词 γ-氨基丁酸受体亚基α-3 膀胱癌 T24细胞 凋亡 迁移 侵袭 AKT/mTOR信号通路
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PIK3CA突变与乳腺癌临床病理特征及预后的相关性
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作者 依合里曼·买买提 曹燕珍 +2 位作者 王翠翠 岳娜 梁莉萍 《基础医学与临床》 2024年第3期303-307,共5页
目的探讨乳腺癌标本中磷脂酰肌醇激酶-3-催化亚基α(PIK3CA)突变与侵袭性乳腺癌临床病理特征及预后的相关性。方法收集2018年1月至2020年1月确诊为乳腺癌的181例患者临床病理资料,用免疫组织化学(IHC)法检测乳腺癌雌激素受体(ER)、孕激... 目的探讨乳腺癌标本中磷脂酰肌醇激酶-3-催化亚基α(PIK3CA)突变与侵袭性乳腺癌临床病理特征及预后的相关性。方法收集2018年1月至2020年1月确诊为乳腺癌的181例患者临床病理资料,用免疫组织化学(IHC)法检测乳腺癌雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER2)、Ki-67等指标,RT-qPCR检测乳腺癌中PIK3CA外显子9(exon9)和外显子20(exon20)的突变。结果181例侵袭性乳腺癌中PIK3CA突变70例,其中31例(44.28%)exon9突变、39例(55.71%)exon20突变。PIK3CA突变与乳腺癌分子分型有明显差异(P<0.05)。PIK3CA突变与乳腺癌的Ki67表达有明显差异(P<0.05)。34例(48.57%)HR+/HER2-组PIK3CA突变,36例(51.43%)非HR+/HER2-组突变,二者PIK3CA突变分布有明显差异(P<0.05)。PIK3CA突变患者病死率高于PIK3CA野生型(P<0.05)。结论PIK3CA突变与乳腺癌分子分型、Ki67增值指数及预后相关,可为患者精准治疗提供参考。 展开更多
关键词 乳腺癌 磷脂酰肌醇激酶-3-催化亚基α(PIK3CA) 雌激素受体 孕激素受体 人表皮生长因子受体2
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MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons 被引量:4
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作者 Bhupender Sharma Melissa MTorres +2 位作者 Sheryl Rodriguez Laxman Gangwani Subodh Kumar 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第12期2698-2707,共10页
Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's dis... Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's disease-related dementia.Our previous study identified the upregulation of microRNA-502-3p(miR-502-3p)and downregulation of GABA type A receptor subunitα-1 in Alzheimer's disease synapses.This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function.In vitro studies were perfo rmed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs.In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunitα-1 mRNA.Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunitα-1 gene and suppresses the luciferase activity.Furthermore,quantitative reve rse transcription-polymerase chain reaction,miRNA in situ hybridization,immunoblotting,and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunitα-1 level,while suppression of miR-502-3p increased the level of GABA type A receptor subunitα-1 protein.Notably,as a result of the overexpression of miR-502-3p,cell viability was found to be reduced,and the population of necrotic cells was found to be increased.The whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney(HEK)recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function,suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function.Additionally,the levels of proteins associated with Alzheimer s disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression.The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p.We propose that micro-RNA,in particular miR-502-3p,could be a potential therapeutic to rget to modulate GABAergic synapse function in neurological disorders,including Alzheimer's disease and Alzheimer's diseaserelated dementia. 展开更多
关键词 Alzheimer's disease GABAergic synapse gamma-aminobutyric acid type A receptor subunitα-1(GABRα1) microRNA-502-3p(miR-502-3p) miRNA in situ hybridization PATCH-CLAMP
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STAT3 ameliorates truncated tau-induced cognitive deficits 被引量:2
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作者 Bingge Zhang Huali Wan +7 位作者 Maimaitijiang Maierwufu Qian Liu Ting Li Ye He Xin Wang Gongping Liu Xiaoyue Hong Qiong Feng 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第4期915-922,共8页
Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s dis... Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology. 展开更多
关键词 Alzheimer’s disease apoptosis cognitive deficit memory neurodegenerative disease neuron loss n-methyl-d-aspartic acid receptor STAT3 SYNAPSE tau-N368
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食管鳞癌组织中EGFR、KRAS及PIK3CA基因突变的检测及其临床意义分析
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作者 古丽亚·买买提 孟存仁 +3 位作者 刘清 郑树涛 卢晓梅 刘涛 《中国医刊》 CAS 2024年第2期163-168,共6页
目的分析食管鳞癌组织中表皮生长因子受体(EGFR)、Kirsten鼠类肉瘤病毒癌基因(KRAS)和磷脂酰肌醇3激酶(PIK3CA)基因的突变情况及其与患者临床特征的关系。方法选取2006年1月至2012年12月在新疆医科大学第一附属医院确诊的210例食管鳞癌... 目的分析食管鳞癌组织中表皮生长因子受体(EGFR)、Kirsten鼠类肉瘤病毒癌基因(KRAS)和磷脂酰肌醇3激酶(PIK3CA)基因的突变情况及其与患者临床特征的关系。方法选取2006年1月至2012年12月在新疆医科大学第一附属医院确诊的210例食管鳞癌患者的组织标本进行DNA提取和目标位点扩增,再利用一代测序的方法对EGFR18号和21号外显子、KRAS2号外显子、PIK3CA9号外显子进行测序,探讨各基因突变情况及其与临床病理特征的关系,并分析不同基因突变之间的相关性。结果210例食管鳞癌标本中EGFR基因突变率为27.14%,KRAS基因突变率为14.29%,PIK3CA基因突变率为18.59%,EGFR和KRAS双基因联合突变率为4.76%,EGFR和PIK3CA双基因联合突变率为5.71%,EGFR、KRAS、PIK3CA三基因联合突变率为1.43%。EGFR基因突变与性别、肿瘤直径、分化程度具有相关性(P<0.05),KRAS基因突变与肿瘤直径、分化程度、T分期、临床分期具有相关性(P<0.05),PIK3CA基因突变与性别、肿瘤直径、分化程度具有相关性(P<0.05),EGFR和PIK3CA联合突变与性别、肿瘤直径、分化程度具有相关性(P<0.05)。EGFR基因突变与KRAS基因突变具有相关性(P<0.05),而EGFR基因突变与PIK3CA基因突变之间无相关性(P>0.05)。结论食管鳞癌组织中EGFR基因突变率最高,PIK3CA基因突变率次之,KRAS基因突变率最低;EGFR与KRAS或PIK3CA基因突变联合检测具有一定的临床意义。 展开更多
关键词 食管鳞癌 表皮生长因子受体 Kirsten鼠类肉瘤病毒癌基因 磷脂酰肌醇3激酶
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当归补血汤对2型糖尿病大鼠IRS-1/PI3K/Akt2信号通路的影响研究 被引量:5
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作者 尹世伟 崔玉兰 +3 位作者 贾小玉 赵婷 崔宇晖 康丽艳 《现代中西医结合杂志》 CAS 2022年第10期1369-1374,1395,共7页
目的探讨当归补血汤对2型糖尿病大鼠胰岛素受体底物1(IRS-1)、磷脂酰肌醇3激酶p85亚基(PI3Kp85)、蛋白激酶B(Akt2)表达的影响。方法取8只雄性ZDF(fa/+)大鼠作为对照组;另取24只雄性ZDF(fa/fa)大鼠给予3周高脂饲料建立2型糖尿病模型,然... 目的探讨当归补血汤对2型糖尿病大鼠胰岛素受体底物1(IRS-1)、磷脂酰肌醇3激酶p85亚基(PI3Kp85)、蛋白激酶B(Akt2)表达的影响。方法取8只雄性ZDF(fa/+)大鼠作为对照组;另取24只雄性ZDF(fa/fa)大鼠给予3周高脂饲料建立2型糖尿病模型,然后将造模成功大鼠随机分为模型组、盐酸二甲双胍组、当归补血汤组,每组8只。盐酸二甲双胍组给予盐酸二甲双胍肠溶片300 mg/kg灌胃,当归补血汤组给予当归补血汤(配方颗粒加蒸馏水配制)12.8 g/kg灌胃,对照组和模型组给予等量生理盐水灌胃,均1次/d,连续8周。末次灌胃后,禁食14 h进行口服葡萄糖耐量试验,计算胰岛素生成指数、胰岛素抵抗指数(HOMA-IR)和胰岛β细胞功能指数(HOMA-β);糖耐量试验结束后隔天禁食12 h抽取腹主动脉血,检测丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平;取各组大鼠肝脏组织,采用RT-qPCR法检测IRS-1、PI3Kp85和Akt2 mRNA表达情况,采用Western blot法检测IRS-1、p-IRS1、PI3Kp85、p-PI3Kp85、Akt2、p-Akt2蛋白表达情况。结果模型组大鼠空腹血糖水平、空腹胰岛素水平、血糖曲线下面积、HOMA-IR均明显高于对照组(P均<0.05),胰岛素生成指数、HOMA-β均明显低于对照组(P均<0.05);盐酸二甲双胍组和当归补血汤组空腹血糖水平、空腹胰岛素水平、血糖曲线下面积、HOMA-IR均明显低于模型组(P均<0.05),胰岛素生成指数、HOMA-β均明显高于模型组(P均<0.05),当归补血汤组各指标改善情况均明显优于二甲双胍组(P均<0.05)。与对照组比较,模型组大鼠血清ALT、AST、TC、TG、LDL-C水平均明显升高(P均<0.05),HDL-C水平明显降低(P<0.05);与模型组比较,盐酸二甲双胍组和当归补血汤组大鼠血清ALT、AST、TC、TG、LDL-C水平均明显降低(P均<0.05),HDL-C水平均明显降低(P均<0.05);除ALT、TC外,其余指标当归补血汤组改善情况均明显优于盐酸二甲双胍组(P均<0.05)。模型组大鼠肝脏组织中IRS-1、PI3Kp85、Akt2 mRNA表达量和IRS-1、p-IRS1、PI3Kp85、p-PI3Kp85、Akt2、p-Akt2蛋白表达量均明显低于对照组(P均<0.05),盐酸二甲双胍组和当归补血汤组上述各指标表达量均明显高于模型组(P均<0.05);除Akt2 mRNA、p-Akt2外,其余指标当归补血汤组均明显高于盐酸二甲双胍组(P均<0.05)。结论当归补血汤可能通过调节IRS-1/PI3K/Akt2信号通路发挥治疗2型糖尿病的作用。 展开更多
关键词 当归补血汤 2型糖尿病 大鼠 胰岛素受体底物1 磷脂酰肌醇3激酶p85亚基 蛋白激酶B
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IL-3Rα在急性白血病中的表达及意义
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作者 彭鹏 宋玉华 《重庆医学》 CAS CSCD 北大核心 2012年第36期3840-3842,共3页
目的探讨白细胞介素-3受体α亚基(IL-3Rα)在急性白血病(AL)中的表达及意义。方法建立AL患者标本,采用逆转录-聚合酶链反应(RT-PCR)方法检测IL-3Rα的表达,分别予以观察IL-3RαmRNA表达与AL和CD34的相关性。结果对照组未检测到IL-3Rα表... 目的探讨白细胞介素-3受体α亚基(IL-3Rα)在急性白血病(AL)中的表达及意义。方法建立AL患者标本,采用逆转录-聚合酶链反应(RT-PCR)方法检测IL-3Rα的表达,分别予以观察IL-3RαmRNA表达与AL和CD34的相关性。结果对照组未检测到IL-3Rα表达;AML和B-ALL患者IL-3Rα阳性表达显著高于对照组,T-ALL患者未检测到IL-3Rα的表达,M1~M5各型患者的阳性率差异无统计学意义(P>0.05);AML和B-ALL患者的IL-3Rα阳性表达与CD34显著相关,差异有统计学意义(P<0.05);患者中IL-3Rα阳性表达的患者CR率低于阴性者,且与外周血白细胞计数、骨髓中原始细胞比例有关。结论 IL-3Rα在AML和B-ALL发病中有一定作用,检测IL-3Rα有助于ALL的T和B两型的鉴别。IL-3Rα基因可能是AML、B-ALL的一个不良预后因素。 展开更多
关键词 白细胞介素3受体α亚单位 急性白血病 基因
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人类IL-3受体α亚单位与小鼠AIC2B蛋白的相互作用
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作者 张日 朱子玲 +1 位作者 常伟荣 John F.DiPersio 《苏州医学院学报》 2000年第10期882-884,共3页
目的 探索人类IL - 3受体 (IL - 3R)α亚单位与小鼠内源性AIC2B蛋白在诱导细胞增殖信号表达过程中的相互作用。方法 通过PCR扩增技术 ,构建了IL - 3Rα亚单位胞浆域缺失突变子 34、2 2和CD ,然后将野生型和突变型IL - 3Rα亚单位cDNA... 目的 探索人类IL - 3受体 (IL - 3R)α亚单位与小鼠内源性AIC2B蛋白在诱导细胞增殖信号表达过程中的相互作用。方法 通过PCR扩增技术 ,构建了IL - 3Rα亚单位胞浆域缺失突变子 34、2 2和CD ,然后将野生型和突变型IL - 3Rα亚单位cDNA分别转染到含小鼠IL - 3R基因表达的BaF3细胞 ,并检测了阳性转染子的增殖信号传导和酪氨酸磷酸化。结果 表达野生型hIL - 3Rα/ βc的BaF3阳性对照克隆在生理浓度hIL - 3诱导后即可出现细胞增殖和胞浆信号蛋白 βc、Jak2及Shc磷酸化 ;而含野生型IL - 3Rα亚单位和AIC2B的BaF3细胞可出现高浓度hIL - 3刺激的细胞增殖反应 ,但无信号传导分子的活化 ;共表达突变型IL - 3Rα与AIC2B的BaF3细胞及未转染的BaF3细胞则对各种浓度的hIL - 3刺激均无反应。结论 尽管hIL - 3Rβc亚单位在hIL - 3诱导的信号传导过程中担负关键作用 ,但小鼠内源性AIC2B也可与hIL - 3Rα重建功能性hIL - 3R ,这种功能的表达需要hIL - 展开更多
关键词 IL-3受体 Α亚单位 相互作用 小鼠 人类 IL-3R hIL-3 PCR扩增技术 酪氨酸磷酸化 增殖信号传导 信号传导分子 细胞增殖反应 野生型 缺失突变 基因表达 cDNA 信号蛋白 生理浓度 阳性对照 结果表达 Jak2 a亚单位 受体分子
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Neuroprotective effects of autophagy inhibition on hippocampal glutamate receptor subunits after hypoxia-ischemia-induced brain damage in newborn rats 被引量:14
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作者 Li-xiao Xu Xiao-juan Tang +8 位作者 Yuan-yuan Yang Mei Li Mei-fang Jin Po Miao Xin Ding Ying Wang Yan-hong Li Bin Sun Xing Feng 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第3期417-424,共8页
Autophagy has been suggested to participate in the pathology of hypoxic-ischemic brain damage(HIBD).However,its regulatory role in HIBD remains unclear and was thus examined here using a rat model.To induce HIBD,the... Autophagy has been suggested to participate in the pathology of hypoxic-ischemic brain damage(HIBD).However,its regulatory role in HIBD remains unclear and was thus examined here using a rat model.To induce HIBD,the left common carotid artery was ligated in neonatal rats,and the rats were subjected to hypoxia for 2 hours.Some of these rats were intraperitoneally pretreated with the autophagy inhibitor 3-methyladenine(10 m M in 10 μL) or the autophagy stimulator rapamycin(1 g/kg) 1 hour before artery ligation.Our findings demonstrated that hypoxia-ischemia-induced hippocampal injury in neonatal rats was accompanied by increased expression levels of the autophagy-related proteins light chain 3 and Beclin-1 as well as of the AMPA receptor subunit GluR 1,but by reduced expression of GluR 2.Pretreatment with the autophagy inhibitor 3-methyladenine blocked hypoxia-ischemia-induced hippocampal injury,whereas pretreatment with the autophagy stimulator rapamycin significantly augmented hippocampal injury.Additionally,3-methyladenine pretreatment blocked the hypoxia-ischemia-induced upregulation of Glu R1 and downregulation of GluR2 in the hippocampus.By contrast,rapamycin further elevated hippocampal Glu R1 levels and exacerbated decreased GluR2 expression levels in neonates with HIBD.Our results indicate that autophagy inhibition favors the prevention of HIBD in neonatal rats,at least in part,through normalizing Glu R1 and GluR2 expression. 展开更多
关键词 nerve regeneration hypoxic-ischemic brain damage hypoxia ischemia α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor subunit GluR hippocampus RAPAMYCIN 3-methyladenine neural regeneration
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囊泡膜谷氨酸转运体与ASIC3或TRPV1在大鼠结状神经节内的共存研究(英文)
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作者 李志红 蒋兴旺 +1 位作者 葛顺楠 李金莲 《神经解剖学杂志》 CAS CSCD 北大核心 2009年第6期621-625,共5页
为了探讨囊泡膜谷氨酸转运体(VGluTS)与酸敏感离子通道亚基3(ASIC3)或瞬时感受器电位香草酸亚型1(TRPV1)样阳性产物在大鼠迷走神经结状神经节(nodoseganglia,NG)内的分布和共存,本研究采用免疫荧光组织化学双重标记技术,在激光共聚焦显... 为了探讨囊泡膜谷氨酸转运体(VGluTS)与酸敏感离子通道亚基3(ASIC3)或瞬时感受器电位香草酸亚型1(TRPV1)样阳性产物在大鼠迷走神经结状神经节(nodoseganglia,NG)内的分布和共存,本研究采用免疫荧光组织化学双重标记技术,在激光共聚焦显微镜下观察了大鼠NG内VGluT1或VGluT2分别与ASIC3或TRPV1的共存情况。结果显示:(1)在NG内,VGluT2、ASIC3和TRPV1主要见于中、小型神经元的胞浆内,大型神经元少见,而VGluT1阳性神经元数量较少,主要见于大型或中型神经元;(2)部分VGluT2阳性神经元同时显示ASIC3或TRPVl免疫活性,其中VGluT2/ASIC3双标神经元分别占VGluT2阳性神经元的43.06%,占ASIC3阳性神经元的58.74%;而VGluT2/TRPVl双标神经元分别占VGluT2或TRPVl阳性神经元的5617%和51.12%;(3)VGluTI与ASIC3或TRPV1双标神经元的数量很少,不到1%。以上结果提示,VGluT2主要存在于NG内中、小型神经元,这些神经元通常被认为是内脏伤害性信息的初级感受神经元,因而VGluT2分别与ASIC3或TRPVl的共存表明它们可能与内脏伤害性信息的产生和传递密切相关。 展开更多
关键词 囊泡膜谷氨酸转运体 酸敏感离子通道亚基3 瞬时感受器电位香草酸亚型1 免疫荧光组织化学 结状神经节大鼠
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BRCC3/NLRP3促进子宫内膜异位症炎癌转化中的机制 被引量:3
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作者 刘彧 吴琼蔚 +5 位作者 张文璎 王春春 黄玉华 李冰 马成斌 杨钰 《中国肿瘤生物治疗杂志》 CAS CSCD 北大核心 2023年第1期35-41,共7页
目的:探讨NOD样受体蛋白3(NLRP3)炎症小体的活化在子宫内膜异位症(EMT)进展为EMT相关性卵巢癌(EAOC)过程中的作用及其机制。方法:选取2018年4月至2019年6月上海市长宁区幼保健院收治的EAOC、EMT、正常子宫内膜(CON组)组织标本各15例及... 目的:探讨NOD样受体蛋白3(NLRP3)炎症小体的活化在子宫内膜异位症(EMT)进展为EMT相关性卵巢癌(EAOC)过程中的作用及其机制。方法:选取2018年4月至2019年6月上海市长宁区幼保健院收治的EAOC、EMT、正常子宫内膜(CON组)组织标本各15例及患者的临床资料,利用免疫组织化学染色法、WB法检测EAOC、EMT和CON组织中NLRP3、caspase-1和IL-1β及含BRCA1/BRCA2的复杂亚基3(BRCC3)的表达水平。构建过表达BRCC3质粒和si-NLRP3质粒并转染EMT细胞CRL-7566,通过WB法检测转染后细胞中BRCC3蛋白的表达水平,利用MTT法、流式细胞术及Transwell实验分别检测转染后细胞增殖、凋亡、迁移与侵袭能力的变化。对过表达BRCC3组细胞进行干扰NLRP3实验,通过WB法检测干扰后BRCC3和NLRP3蛋白的表达水平,检测干扰后细胞增殖、凋亡、迁移与侵袭能力的变化。结果:EAOC和EMT组织中NLRP3、caspase-1、IL-1β和BRCC3的表达水平较CON组均呈明显升高(均P<0.01),且EAOC组织中NLRP3与BRCC3的表达呈正相关(r=0.65,P<0.01)。在CRL-7566细胞中过表达BRCC3显著促进细胞的增殖、迁移和侵袭并抑制细胞凋亡(均P<0.01),敲减NLRP3则抑制CRL-7566细胞的上述表型(均P<0.01),过表达BRCC3增强NLRP3的表达水平(P<0.01),而干扰BRCC3则抑制NLRP3表达(P<0.01);干扰NLRP3可以部分逆转BRCC3对细胞凋亡的抑制作用(P<0.01)、对细胞迁移(P<0.05)和侵袭(P<0.01)的促进作用。结论:EAOC和EMT组织中NLRP3和BRCC3均呈高表达,过表达BRCC3可促进CRL-7566细胞的增殖、迁移和侵袭并抑制细胞凋亡,与EMT向EAOC转化有关,BRCC3/NLRP3是潜在的EAOC炎癌转化预测标志物及治疗靶点。 展开更多
关键词 子宫内膜异位症 子宫内膜异位症相关的卵巢癌 NOD样受体蛋白3 含BRCA1/BRCA2的复杂亚基3 CRL-7566细胞 增殖 迁移 侵袭 凋亡
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磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α通过调控跨膜受体蛋白1对子宫内膜癌病人中性粒细胞的影响 被引量:1
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作者 李儒彩 黄成谋 +2 位作者 李静 郭丽娟 潘英连 《安徽医药》 CAS 2023年第4期733-737,共5页
目的探究磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α(PIK3CA)基因通过调控跨膜受体蛋白1(Notch1)的表达对子宫内膜癌病人血中性粒细胞的影响。方法选择2020年3月至2021年9月在海南医学院第一附属医院接受治疗的50例子宫内膜癌病人(病例组)... 目的探究磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α(PIK3CA)基因通过调控跨膜受体蛋白1(Notch1)的表达对子宫内膜癌病人血中性粒细胞的影响。方法选择2020年3月至2021年9月在海南医学院第一附属医院接受治疗的50例子宫内膜癌病人(病例组)和50例健康女性(对照组)为分析对象。检测病例组和实验组血清中中性粒细胞(NE)、淋巴细胞(LY)、血红蛋白(Hb)、血小板(PLT),计算NLR指数(中性粒细胞计数/淋巴细胞计数)。逆转录PCR(RT-PCR)和Western blotting检测PIK3CA和Notch1的相对表达量。选取人原髓细胞白血病细胞/全反式维甲酸细胞(HL-60/ATRA细胞),在不同时间下进行培养,验证PIK3CA通过Notch1对NE的影响。结果病例组病人NE、LY、PLT指标以及NLR指数为(6.03±0.40)×10^(9)/L、(2.15±0.31)×10^(9)/L、(257.40±37.51)×10^(9)/L、(3.69±0.41)分别高于对照组的(5.13±0.50)×10^(9)/L、(1.68±0.16)×10^(9)/L、(202.10±23.39)×10^(9)/L、(2.44±0.39),病例组病人Hb水平为(138.72±13.79)g/L低于对照组Hb水平(149.52±10.65)g/L,说明子宫内膜癌病人炎症微环境异常。病例组PIK3CA和Notch1相对表达量为(3.351±0.496)、(3.467±0.440)高于对照组的(1.581±0.275)、(1.519±0.279)。HL-60/ATRA细胞培养实验验证了PIK3CA高表达促进Notch1高表达进而抑制NE的增殖。结论在NE中,Notch1表达量随着PIK3CA表达量升高而升高,NE细胞活力逐渐下降,初步证实了PIK3CA基因通过调控Notch1的表达对子宫内膜癌中NE产生影响。 展开更多
关键词 子宫内膜肿瘤 细胞增殖 磷脂酰肌醇-4 5-二磷酸3-激酶催化亚基α(PIK3CA) 跨膜受体蛋白1 中性粒细胞
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外周血核心结合因子-β核苷酸结合寡聚化结构域样受体3组织抑制剂在膝骨关节炎中的表达及与病情的相关性分析 被引量:1
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作者 张蒙 朱志强 王森 《实用医技杂志》 2022年第8期814-817,共4页
目的分析外周血核心结合因子-β(Cbf-β)、核苷酸结合寡聚化结构域样受体3(NLRP3)、组织抑制剂(TIMP-1)在膝骨关节炎中的表达及与病情的相关性。方法选取2021年2月至2022年2月河南神火集团总医院收治的膝骨关节炎患者150例设为研究组,... 目的分析外周血核心结合因子-β(Cbf-β)、核苷酸结合寡聚化结构域样受体3(NLRP3)、组织抑制剂(TIMP-1)在膝骨关节炎中的表达及与病情的相关性。方法选取2021年2月至2022年2月河南神火集团总医院收治的膝骨关节炎患者150例设为研究组,另选取同期在河南神火集团总医院进行体检的健康人群150名设为对照组。分析2组人群外周血Cbf-β、NLRP3、TIMP-1水平表达情况。使用磁共振成像对患者进行检测,随后按照Recht标准将膝骨关节炎分为四级,即Ⅰ、Ⅱ、Ⅲ、Ⅳ级,分析不同病情下患者外周血Cbf-β、NLRP3、TIMP-1水平表达情况及三者的相关性。结果与对照组相比,研究组Cbf-β、TIMP-1水平较高,NLRP3水平较低,差异具有统计学意义(P<0.05);与Ⅰ级患者相比,Ⅱ级、Ⅲ级、Ⅳ级患者Cbf-β、TIMP-1水平呈不断上升趋势,NLRP3呈不断下降的趋势,差异具有统计学意义(P<0.05);Cbf-β、NLRP3呈负相关(r=-9.068,P=0.003);Cbf-β、TIMP-1呈正相关(r=11.830,P=0.001);NLRP3、TIMP-1呈负相关(r=-22.820,P=0.001);Cbf-β、TIMP-1与膝骨关节Recht等级呈正相关;NLRP3与膝骨关节炎Recht等级呈负相关。结论外周血Cbf-β、NLRP3、TIMP-1在膝骨关节炎中呈现出异常表达,三者在膝骨关节炎中存在着相关性,且Cbf-β、TIMP-1与膝骨关节Recht等级呈正相关;NLRP3与膝骨关节炎Recht等级呈负相关。说明三者与膝骨关节炎密切相关,对其检测有着一定的诊断价值。 展开更多
关键词 膝骨关节炎 核心结合因子β亚基 核苷酸结合寡聚化结构域样受体3 组织抑制剂
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N-methyl-D-aspartic acid receptor 1 (NMDAR1) aggravates secondary inflammatory damage induced by hemin-NLRP3 pathway after intracerebral hemorrhage 被引量:12
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作者 Xun Weng Yan Tan Xiang Chu Xiao-Feng Wu Rui Liu Yue Tian Lin Li Feng Guo Qing Ouyang Lei Li 《Chinese Journal of Traumatology》 CAS CSCD 2015年第5期254-258,共5页
Objective: Inflammation plays a critical role in secondary brain damage after intracerebral hemorrhage (ICH). However, the mechanisms of inflammatory injury following ICH are still unclear, particularly the involve... Objective: Inflammation plays a critical role in secondary brain damage after intracerebral hemorrhage (ICH). However, the mechanisms of inflammatory injury following ICH are still unclear, particularly the involvement of NLRP3 inflammasome, which are crucial to sterile inflammatory responses. In this study, we aim to test the hypothesis that NLRP3 signaling pathway takes a vital position in ICH-induced sec- ondary inflammatory damage and detect the role of N-methyl-D-aspartic acid receptor 1 (NMDARI) in this progress. Methods: ICH was induced in mice by microinjection of heroin into the striatum. The protein levels of NMDAR1, NMDAR1 phosphorylation, NLRP3 and IL-113 were measured by Western blot. The binding of NMDARI to NLRP3 was detected by immunoprecipitation. Results: The expression of NMDARI, NMDAR1 phosphorylation, NLRP3 and IL-I ~ were rapidly increased after ICH. Heroin treatment enhanced NMDAR1 expression and NMDAR1 phosphorylation, as well in cultured microglial cells treated by hemin. Hemin up-regulated NLRP3 and IL-I]3 level, which was reversed by MK801 (NMDAR antagonist) in vitro. Hemin also promoted the binding of NMDAR1 to NLRP3. Conclusion: Our findings suggest that NMDARI plays a pivotal role in hemin-induced NLRP3-mediated inflammatory damage through synergistic activation. 展开更多
关键词 HEMIN MICROGLIA NLRP3 protein n-methyl-d-aspartic acid receptor 1 INFLAMMASOME
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泛癌分析揭示SREK1在低级别胶质瘤中促进CD274表达
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作者 刘东 刘媛 +1 位作者 张淑灵 王玉祥 《宁夏医科大学学报》 2024年第9期893-902,910,共11页
目的剪接调节谷氨酸和富赖氨酸的蛋白质1(SREK1)在多种肿瘤中的泛癌分析,揭示SREK1在泛癌中的作用。方法利用在线数据库GEPIA 2、TIMER 2.0、TISIDB和cBioPortal分析SREK1表达对肿瘤患者预后的影响、在低级别胶质瘤(LGG)肿瘤组织中的表... 目的剪接调节谷氨酸和富赖氨酸的蛋白质1(SREK1)在多种肿瘤中的泛癌分析,揭示SREK1在泛癌中的作用。方法利用在线数据库GEPIA 2、TIMER 2.0、TISIDB和cBioPortal分析SREK1表达对肿瘤患者预后的影响、在低级别胶质瘤(LGG)肿瘤组织中的表达、遗传变异的特征及其表达对肿瘤组织中免疫细胞的浸润和免疫—肿瘤靶基因的相关性分析。结果LGG肿瘤组织中,SREK1表达与记忆B细胞、活化的CD4+T细胞、Th2细胞、中性粒细胞、NKT细胞以及单核细胞和CD56dimNK细胞的浸润存在相关性(P均<0.05)。SREK1与免疫—肿瘤靶基因如信号传导及转录激活蛋白3(STAT3)、Ⅰ型干扰素受体1(IFNAR1)、核受体亚家族3C组成员1(NR3C1)和表皮生长因子受体(EGFR)、表面抗原分化簇274(CD274)等表达在LGG中均呈正相关(P均<0.05)。结论SREK1是LGG患者的危险因子之一,可能通过促进CD274的表达来加剧LGG的进展。 展开更多
关键词 剪接调节谷氨酸和富赖氨酸的蛋白质1 低级别胶质瘤 细胞程序性死亡-配体1 Ⅰ型干扰素受体1 信号转导和转录激活因子3 免疫—肿瘤靶基因
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