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B2 adrenergic receptors and morphological changes of the enteric nervous system in colorectal adenocarcinoma 被引量:2
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作者 Raluca Niculina Ciurea Ion Rogoveanu +7 位作者 Daniel Pirici Georgica-Costinel Tartea Costin Teodor Streba Cristina Florescu Bogdan Catalin Ileana Puiu Elena-Anca Tartea Cristin Constantin Vere 《World Journal of Gastroenterology》 SCIE CAS 2017年第7期1250-1261,共12页
To study the morphology of the enteric nervous system and the expression of beta-2 adrenergic (B2A) receptors in primary colorectal cancer.METHODSIn this study, we included forty-eight patients with primary colorectal... To study the morphology of the enteric nervous system and the expression of beta-2 adrenergic (B2A) receptors in primary colorectal cancer.METHODSIn this study, we included forty-eight patients with primary colorectal cancer and nine patients for control tissue from the excision of a colonic segment for benign conditions. We determined the clinicopathological features and evaluated the immunohistochemical expression pattern of B2A receptors as well as the morphological changes of the enteric nervous system (ENS). In order to assess statistical differences, we used the student t-test for comparing the means of two groups and one-way analysis of variance with Bonferroni’s post hoc analysis for comparing the means of more than two groups. Correlations were assessed using the Pearson’s correlation coefficient.RESULTSB2A receptors were significantly associated with tumor grading, tumor size, tumor invasion, lymph node metastasis (P < 0.05), while there were no statistically significant associations with gender, CRC location and gross appearance (P > 0.05). We observed, on one hand, a decrease of the relative area for both Auerbach and Meissner plexuses with the increase of the tumor grading, and on the other hand, an increase of the relative area of other nervous elements not in the Meissner plexus or in the Auerbach plexus with the tumor grading. For G1 tumors we found that epithelial B2A area showed an inverse correlation with the Auerbach plexus areas [r(14) = -0.531, P < 0.05], while for G2 tumors, epithelial B2A areas showed an indirect variation with both the Auerbach plexus areas [r(14) = -0.453, P < 0.05] and the Meissner areas [r(14) = -0.825, P < 0.01]. For G3 tumors, the inverse dependence increased for both Auerbach [r(14) = -0.587, P < 0.05] and Meissner [r(14) = -0.934, P < 0.05] plexuses.CONCLUSIONB2A receptors play an important role in colorectal carcinogenesis and can be utilized as prognostic factors. Furthermore, study of the ENS in colorectal cancer may lead to targeted molecular therapies. 展开更多
关键词 beta-2 adrenergic receptors Enteric nervous system Colorectal adenocarcinoma Spectral unmixing immunohistochemistry Tumor grading
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Blocking beta 2-adrenergic receptor inhibits dendrite ramification in a mouse model of Alzheimer's disease 被引量:3
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作者 Qin Wu Jin-xia Sun +4 位作者 Xiang-he Song Jing Wang Cun-quan Xiong Fei-xiang Teng Cui-xiang Gao 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第9期1499-1506,共8页
Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer's disease (AD), although the ... Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer's disease (AD), although the mechanism involved is still poorly understood. The current study investigated the potential effect of the selective β2-adrenergic receptor antagonist, ICI 118551 (ICI), on Aβ deposits and AD-related cognitive impairment. Morris water maze test results demonstrated that the performance of AD-transgenic (TG) mice treated with ICI (AD-TG/ICI) was significantly poorer compared with NaCl-treated AD-TG mice (AD-TG/NaCl), suggesting that β2-adrenergic receptor blockage by ICI might reduce the learning and memory abilities of mice. Golgi staining and immunohistochemical staining revealed that blockage of the β2-adrenergic receptor by ICI treatment decreased the number of dendritic branches, and ICI treatment in AD-TG mice decreased the expression of hippocampal synaptophysin and synapsin 1. Western blot assay results showed that the blockage of β2-adrener- gic receptor increased amyloid-β accumulation by downregulating hippocampal a-secretase activity and increasing the phosphorylation of amyloid precursor protein. These findings suggest that blocking the β2-adrenergic receptor inhibits dendrite ramification of hippocampal neurons in a mouse model of AD. 展开更多
关键词 nerve regeneration NEURODEGENERATION beta-2 adrenergic receptor Alzheimer's disease amyloid-β ICI 118551 cognitive function dendrite ramification synapsin 1 SYNAPTOPHYSIN a-secretase amyloid precursor protein neural regeneration
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Association of β3 Adrenergic Receptor and Peroxisome Proliferator-activated Receptor Gamma 2 Polymorphisms With Insulin Sensitivity:A Twin Study 被引量:3
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作者 TIAN-JIAO CHEN CHENG-YE JI +1 位作者 XIAO-YING ZHENG AND YONG-HUAHU 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2007年第2期99-105,共7页
Objective To study the effect of β3 adrenergic receptor (β3AR) Trp64Arg and peroxisome proliferator activated receptor gamma 2 (PPAR72) Prol2Ala polymorphisms on insulin resistance. Methods One hundred and eight... Objective To study the effect of β3 adrenergic receptor (β3AR) Trp64Arg and peroxisome proliferator activated receptor gamma 2 (PPAR72) Prol2Ala polymorphisms on insulin resistance. Methods One hundred and eight dizygotic twin pairs were enrolled in this study. Microsatellite polymorphism was used to diagnose zygosity of twins. Insulin sensitivity was estimated with logarithm transformed homeostasis model assessment (HOMA). PCR-RFLP analysis was performed to detect the variants. As a supplement to the sib-pair method, identity by state (IBS) was used to analyze the association of polymorphisms with insulin sensitivity. Results The genotype frequencies of Trp64Trg, Trp64Arg, and Arg64Arg were 72.3%, 23.8%, and 3.9%, respectively, while the genotype frequencies of Pro12Pro, Pro12Ala, and Ala12Ala were 89.9%, 9.6%, and 0.5%, respectively. For β3AR Trp64Arg the interclass co-twin correlations of Waist-to-hip ratio (WHR), blood glucose (GLU), and insulin (INS), homeostasis model assessment insulin resistance index (HOMA-IR) of the twin pairs sharing 2 alleles of IBS were greater than those sharing 0-1 allele of IBS, and HOMA4R had statistic significance. For PPAR3t2 Prol2Ala most traits of twin pairs sharing 2 alleles of IBS had greater correlations and statistic significance in body mass index (BMI), WHR, percent of body fat (PBF) and GLU, but there were low correlations of either insulin or HOMA-IR of twin pairs sharing 1 or 2 alleles of IBS. The combined effects of the two variations showed less squared significant twin-pair differences of INS and HOMA-IR among twins sharing 4 alleles of IBS. Condusions β3AR Trp64Arg and PPAR),2 Pro 12Ala polymorphisms might be associated with insulin resistance and obesity, and there might be slight synergistic effects between this two gene loci, and further studies are necessary to confirm this finding. 展开更多
关键词 Dizygotic twins beta-3 adrenergic receptor Peroxisome proliferator activated receptor gamma 2 POLYMORPHISM Insulin resistance.
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AduoLa Fuzhenglin Down-regulates Microwave-induced Expression of β_1-adrenergic Receptor and Muscarinic Type 2 Acetylcholine Receptor in Myocardial Cells of Rats 被引量:9
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作者 ZHANG Jing PENG Rui Yun +7 位作者 GAO Ya Bing WANG Shui Ming YANG Lei Lei ZHAO Li DONG Ji YAO Bin Wei CHANG Gong Min XIONG Lu 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2014年第3期204-207,共4页
This paper is aimed to study the effect of ADL on expression of ~z-AR and Mz-AchR in myocardial cells of rats exposed to microwave radiation. Immunohistochemistry, Western blot and image analysis were used to detect t... This paper is aimed to study the effect of ADL on expression of ~z-AR and Mz-AchR in myocardial cells of rats exposed to microwave radiation. Immunohistochemistry, Western blot and image analysis were used to detect the expression of ~I-AR and Mz-AchR in myocardial cells at 7 and 14 d after microwave exposure. The results show that the expression level was higher in microwave exposure group and 0.75 g/(kg.d) ADL group than in sham operation group and significantly lower in 1.5 and 3.0 g/(kg.d) ADL groups than in microwave group. So we have a conclusion that the expression of I^z-AR and Mz-AchR is down-regulated in myocardial cells of rats exposed to microwave radiation. ADL can protect rats against microwave-induced heart tissue injury. 展开更多
关键词 AchR AduoLa Fuzhenglin Down-regulates Microwave-induced Expression of adrenergic receptor and Muscarinic Type 2 Acetylcholine receptor in Myocardial Cells of Rats
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Effects ofβ_2-Adrenergic Antagonist on Cytosolic Ca^(2+) in Ventricular Myocytes from Infarcted Rat Heart 被引量:2
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作者 杨蕙 伍卫 +3 位作者 曾冲 邓春玉 方昶 陈珊茗 《South China Journal of Cardiology》 CAS 2006年第1期10-13,共4页
Objectives To investigate the effects of β2-adrenergic antagonist on cytosolic Ca^2 + ([Ca^2+ ]i) in ventricular myocytes from infarcted rat heart. Methods A ligature was placed around left anterior descending co... Objectives To investigate the effects of β2-adrenergic antagonist on cytosolic Ca^2 + ([Ca^2+ ]i) in ventricular myocytes from infarcted rat heart. Methods A ligature was placed around left anterior descending coronary artery of rat hearts. Rats in the control group were sham-operated. Cardiomyocytes were dissociated at two, four, eight weeks after myocardial infarction (MI) and [Ca^2+]i was measured via fura-2 fluorescence. The response of cardiomyocytes to isoproterenol in presence or absence of betal-adrenergic antagonist atenolol, beta2-adrenergic antagonist ICI118, 551 or non-selective β1, 2- adrenergic antagonists propranolol was examined. Results The followings were found that ICI 118, 551 had no significant effects on the rise of [Ca^2+]i induced by isoproterenol in normal ventricular myocytes (P 〉 0.05), ICI118, 551 only significantly attenuated the rise of [Ca^2+]i induced by isoproterenol at four weeks and eight weeks after MI (24.5%±5.7% vs 57.8% ± 13.2%, P〈 0.01; 12.2%±7.9% vs 44.6%±11.3%, P〈 0.01). Atenolol had suppressive effects only in the control group and the post-MI group of two weeks (P 〈 0.05), and propranolol had suppressive effects in the control and all the three post-MI groups (P 〈 0.01). Conclusions Beta2-adrenergic antagonist ICI118, 551 may exert negative effects on Ca^2+ overload initiated by sympathetic stimulation after MI. 展开更多
关键词 Myocardial infarction Beta2-adrenergic receptor Ventricular myocyte Cytosolic Ca^2
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Effects of anisodamine on pulmonary α_1-adrenergic receptor and phospholipase A, in acute lung injury
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作者 孙耕耘 毛宝龄 吕宝璋 《Journal of Medical Colleges of PLA(China)》 CAS 1999年第1期68-71,共4页
Objective: To imastigate the effects of anisodamine on pulmonary α1- adrenergic receptor andphospholipase A, in acute lung injurg. Methods: Change of α1--adrenergic receptor (al AR ) in lung tissllesduring endotoxin... Objective: To imastigate the effects of anisodamine on pulmonary α1- adrenergic receptor andphospholipase A, in acute lung injurg. Methods: Change of α1--adrenergic receptor (al AR ) in lung tissllesduring endotoxin--induced rat acute lung injury was measured with radioligand biding assay. The effects ofanisodamine on pulmonary α1--AR and phospholipase A2 (PLA2 ) were observed. Results: 1. 4 h after theendotoxin injection, there was a significant decrease in the maximal binding capacity of α1--AR by 34% ascompared with the control group. meanwhile elevated activity of PLA2 in rat lung and reduction of thephospholipids content of cell membrane was found. 2. Anisodamine could attenuate endotoxin--induced acutelung injury in rats. Conclusion: This effect might be related to anisodamine’s blockage of α1--AR andsuppression of PLA2, prevention of membranous phospholipids from degradation. and the reduction ofarachidonic acid release. 展开更多
关键词 ANISODAMINE lung injury ENDOTOXIN α1 --adrenergic receptor phospholipase A_2 RAT
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Jueming Prescription(决明方) Reduces Body Weight by Increasing the mRNA Expressions of Beta3-Adrenergic Receptor and Uncoupling Protein-2 in Adipose Tissue of Diet-Induced Obese Rats 被引量:3
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作者 杨玲 卢坤 +5 位作者 文秀英 刘浩 陈爱萍 许明旺 张泓 余杰 《Chinese Journal of Integrative Medicine》 SCIE CAS 2012年第10期775-781,共7页
Objective: To investigate the antiobesity effect of Jueming Prescription (决明方, JMP), a Chinese herbal medicine formula, and its influence on mRNA expressions of beta3 adrenergic receptor (beta3-AR) and uncoupl... Objective: To investigate the antiobesity effect of Jueming Prescription (决明方, JMP), a Chinese herbal medicine formula, and its influence on mRNA expressions of beta3 adrenergic receptor (beta3-AR) and uncoupling protein-2 (UCP-2) in adipose tissue of diet-induced obese rats. Methods: Fifty male Sprague-Dawley rats were randomly divided into the normal control group (n=8) that was on a standard chow diet, and the obese model group (n=42) that was on a diet of high fat chow. Two weeks after the high fat diet, 29 obese rats in the obese model group were further randomly divided into 3 groups: the untreated obese model group (n=9), the met'formin group (n=10, mefformin 300 mg-kg-1.day-1), and the JMP group (n=10, JMP 4 g.kg-1.dayl). After 8-week treatment, body weight, wet weight of visceral fat, and percentage of body fat (PBF) were measured. The levels of fasting blood glucose, serum lipids, and insulin were assessed, and insulin sensitivity index (ISI) was calculated. The adipose tissue section was stained with hematoxylin-Eosin, and the cellular diameter and quantity of adipocytes were evaluated by light microscopy. The mRNA expressions of beta3-AR and UCP-2 from the pet-renal fat tissue were determined by real-time reverse transcription polymerase chain reaction (RT-PCR). Results: Compared with the obese model group, treatment with JMP resulted in significantly lower body weight, wet weight of visceral fat, PBF, and diameter of adipocytes, and significantly higher level of high-density lipoprotein cholesterol, ISI (all P〈0.01), JMP increased the mRNA expressions of beta3-AR and UCP-2 from pedrenal fat tissue (P〈0.05, P〈0.01). Conclusions: JMP could reduce body weight and adipocyte size; and the effect was associated with the up-regulation of beta3-AR and UCP-2 expressions in the adipose tissue and improvement of insulin sensitivity. 展开更多
关键词 Chinese medicine Jueming Prescription Semen Cassiae obesity beta3 adrenergic receptor uncoupling protein-2
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Yohimbine protects against endotoxin-induced acute lung injury by blockade of alpha 2A adrenergic receptor in rats 被引量:3
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作者 LIN Ying ZHU Xi +3 位作者 YAO Wan-zhen YANG Yan-lin A La-ta CHEN Li 《Chinese Medical Journal》 SCIE CAS CSCD 2011年第7期1069-1074,共6页
Background Alpha 2A adrenergic receptor (AR) is a subtype of (]2 AR belonging to G protein-coupled receptors, and exerts a variety of biological effects. Recent studies have demonstrated that the a2A AR activation ... Background Alpha 2A adrenergic receptor (AR) is a subtype of (]2 AR belonging to G protein-coupled receptors, and exerts a variety of biological effects. Recent studies have demonstrated that the a2A AR activation was closely related with inflammatory reaction. The present study aimed to investigate the influence of a2A AR antagonist, yohimbine, on the severity of endotoxin-induced acute lung injury in rats. 展开更多
关键词 acute lung injury a2A adrenergic receptor inflammatory response
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Dissociation of FK506 Binding Protein 12.6 from Ryanodine Receptor Type 2 Is Regulated by cADPR but not β-Adrenergic Stimulation in Mouse Cardiomyocytes
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作者 Xu Zhang, Zheng Chen, Bin Wei,Lin Miao,Guangju Ji Institute of Biophysics Chinese Academy of Sciences, 15 Datun Rd.Chaoyang District, Beijing 100101, China 《生物物理学报》 CAS CSCD 北大核心 2009年第S1期24-24,共1页
AIMS: β-adrenergic augmentation of Ca2+ sparks and cardiac contractility has been functionally linked to phosphorylation-dependent dissociation of FK506 binding protein 12.
关键词 adrenergic Stimulation in Mouse Cardiomyocytes Dissociation of FK506 Binding Protein 12.6 from Ryanodine receptor Type 2 Is Regulated by cADPR but not FK
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哮喘治疗中β_(2)-AR激动药诱发受体脱敏的发生机制及预防进展
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作者 段俊亚 张岩 +4 位作者 宋桂华 陈小松 郭彦荣 周璇 陈新颖 《中国药房》 CAS 北大核心 2024年第15期1910-1914,共5页
β_(2)-肾上腺素受体(β_(2)-AR)激动药作为治疗支气管哮喘(以下简称“哮喘”)的一线药物,在临床中广泛应用,然而长期使用可导致β_(2)-AR脱敏,降低其临床疗效,致使部分哮喘患者症状控制欠佳。β_(2)-AR激动药引起β_(2)-AR脱敏的机制... β_(2)-肾上腺素受体(β_(2)-AR)激动药作为治疗支气管哮喘(以下简称“哮喘”)的一线药物,在临床中广泛应用,然而长期使用可导致β_(2)-AR脱敏,降低其临床疗效,致使部分哮喘患者症状控制欠佳。β_(2)-AR激动药引起β_(2)-AR脱敏的机制主要包括慢速脱敏(与气道黏膜β_(2)-AR密度减小有关)和快速脱敏(与刺激性G蛋白脱偶联机制有关)。环磷酸腺苷(cAMP)-蛋白激酶A和cAMPcAMP激活的交换蛋白信号通路与β_(2)-AR脱敏过程关系密切。糖皮质激素、过氧化物酶体增殖物激活受体γ激动药、ASM-024、中药单药及成方等与β_(2)-AR激动药联合使用时能改善β_(2)-AR的敏感性,从而更好地控制哮喘症状。 展开更多
关键词 支气管哮喘 β_(2)-肾上腺素受体激动药 脱敏 发生机制 预防作用
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β_(2)-肾上腺素能受体与神经丝在山羊脾中的分布和共定位研究
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作者 李晓萌 窦体馨 +4 位作者 李志伟 叶守冲 杨松桦 徐永平 武永杰 《动物医学进展》 北大核心 2024年第2期48-53,共6页
为探讨肾上腺素能神经与脾功能联系,用免疫组织化学SP法和免疫荧光双标记法观察β_(2)-肾上腺素能受体(β_(2)-AR)和羊脾神经丝(NFs)在山羊脾中的表达分布特点。结果显示,β_(2)-AR免疫反应阳性产物在山羊脾中分布广泛,白髓、红髓、中... 为探讨肾上腺素能神经与脾功能联系,用免疫组织化学SP法和免疫荧光双标记法观察β_(2)-肾上腺素能受体(β_(2)-AR)和羊脾神经丝(NFs)在山羊脾中的表达分布特点。结果显示,β_(2)-AR免疫反应阳性产物在山羊脾中分布广泛,白髓、红髓、中央动脉、被膜、小梁、边缘区均有不同程度的着色,白髓中免疫组化染色阳性相对表达量极显著高于红髓(P<0.01),极极显著高于边缘区和被膜(P<0.001);红髓中免疫组化染色阳性相对表达量极显著高于边缘区和被膜(P<0.01);NFs免疫反应阳性产物在山羊脾中红髓、被膜、小梁、小血管、白髓和边缘区均有不同程度的着色,红髓中免疫组化染色阳性相对表达量显著高于白髓(P<0.05),极显著高于边缘区(P<0.01);被膜中免疫组化染色阳性相对表达量极显著高于边缘区和白髓(P<0.01)。共定位研究表明β_(2)-AR和NFs在3个区域存在共定位关系,在平滑肌细胞构成的被膜和小梁中存在,在富含平滑肌细胞的小血管(如中央动脉)中存在,在T、B淋巴细胞丰富区域(如白髓、红髓和边缘区)存在。表明交感-肾上腺素能神经系统对机体免疫具有调控作用。β_(2)-AR和NFs共定位结构证明脾受到交感-肾上腺素能神经的调控,交感神经纤维通过释放神经递质-去甲肾上腺素,作用于脾上的肾上腺素能受体实现功能调控。 展开更多
关键词 β_(2)-肾上腺素能受体 神经丝蛋白 山羊
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β_(2)肾上腺素受体在erastin诱导的前列腺细胞铁死亡和自噬中的作用及其机制
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作者 黄燕萍 张咪 +4 位作者 曾燕 陈津滢 陈芳芳 吴诗锜 徐晨 《解放军医学杂志》 CAS CSCD 北大核心 2024年第5期570-577,共8页
目的探讨β2肾上腺素受体(ADRB2)在铁死亡激活剂erastin(Era)诱导的前列腺癌细胞铁死亡、自噬中的作用及可能的分子机制。方法取慢病毒或对照感染的PC-3细胞,设置sh-NC组(正常培养)、sh-NC+Era组(10μmol/L Era处理24 h)、sh-ADRB2组(... 目的探讨β2肾上腺素受体(ADRB2)在铁死亡激活剂erastin(Era)诱导的前列腺癌细胞铁死亡、自噬中的作用及可能的分子机制。方法取慢病毒或对照感染的PC-3细胞,设置sh-NC组(正常培养)、sh-NC+Era组(10μmol/L Era处理24 h)、sh-ADRB2组(正常培养)与sh-ADRB2+Era组(10μmol/L Era处理24 h)。采用CCK-8法检测铁死亡激活剂Era和铁死亡抑制剂ferrostatin-1(Fer-1)处理后的细胞存活率,透射电镜观察细胞形态变化,丙二醛(MDA)检测试剂盒检测MDA含量,铁离子比色法检测铁离子含量。Western blotting检测胱氨酸谷氨酸转运体(XCT)、铁蛋白重链1(FTH1)、谷胱甘肽过氧化物酶(GPX4)、p62、LC3、c-Jun N-末端激酶(JNK)、c-Jun、p-c-Jun蛋白表达水平。注射ADRB2敲低的PC-3稳转株,构建裸鼠成瘤模型并用Era处理,分为sh-NC组、sh-NC+Era组、sh-ADRB2组与sh-ADRB2+Era组,每组4只。隔天记录瘤体体积及最终瘤体重量,并采用免疫组化检测ADRB2、JNK、c-Jun、p-c-Jun的表达情况。结果Era处理后PC-3细胞存活率下降(P<0.01),加用Fer-1处理后PC-3细胞存活率恢复(P<0.01)。透射电镜下可见,Era处理后PC-3细胞发生铁死亡和自噬形态学改变,MDA和铁离子含量增高(P<0.05或P<0.01);敲低ADRB2并用Era处理后PC-3细胞存活率进一步下降(P<0.05),MDA和铁离子含量进一步升高(P<0.01),FTH1、XCT、GPX4和LC3蛋白表达水平降低(P<0.05或P<0.01),p62蛋白和JNK通路相关基因JNK、c-Jun、p-c-Jun蛋白表达水平升高(P<0.01);JNK抑制剂处理后,FTH1、XCT和LC3表达水平升高,p62表达水平降低(P<0.01)。PC-3裸鼠模型中,sh-ADRB2+Era组瘤体体积明显小于sh-NC+Era组和sh-ADRB2组(P<0.05或P<0.01);免疫组化检测结果显示,与sh-NC组比较,sh-ADRB2组ADRB2蛋白表达水平降低(P<0.05),JNK、c-Jun和p-c-Jun蛋白表达水平升高(P<0.01);与sh-NC+Era组比较,sh-ADRB2+Era组ADRB2蛋白表达水平降低,JNK、c-Jun和p-c-Jun蛋白表达水平升高(P<0.05)。结论ADRB2可能通过JNK/c-Jun通路调控前列腺癌细胞中Era诱导的铁死亡和自噬。 展开更多
关键词 前列腺癌 β_(2)肾上腺素受体 铁死亡 自噬
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α_(1A)-肾上腺素能受体与增强型绿色荧光蛋白标记的活化T细胞核因子2稳定共表达细胞的构建
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作者 王晓璇 李玉蕾 +1 位作者 周培岚 苏瑞斌 《中国药理学与毒理学杂志》 CAS 北大核心 2024年第8期587-594,共8页
目的建立α_(1A)-肾上腺素能受体(α_(1A)-AR)与增强型绿色荧光蛋白(EGFP)标记的活化T细胞核因子2(NFAT2)稳定共表达细胞。方法①将pcDNA3.1-α_(1A)-AR-3×FLAG重组质粒转染至U2OS-EGFPNFAT2细胞,经潮霉素B(Hygro-B)200 mg·L^... 目的建立α_(1A)-肾上腺素能受体(α_(1A)-AR)与增强型绿色荧光蛋白(EGFP)标记的活化T细胞核因子2(NFAT2)稳定共表达细胞。方法①将pcDNA3.1-α_(1A)-AR-3×FLAG重组质粒转染至U2OS-EGFPNFAT2细胞,经潮霉素B(Hygro-B)200 mg·L^(-1)压力筛选后加入α_(1A)-AR激动剂去甲肾上腺素(NE,10μmol·L^(-1))孵育30 min,通过高内涵筛选系统检测细胞核内绿色荧光强度,验证EGFP-NFAT2核转位,筛选得到稳定表达α_(1A)-AR的U2OS-EGFP-NFAT2-α_(1A)-AR细胞。②采用实时荧光定量PCR(RT-qPCR)和Western印迹法检测该细胞和对照细胞U2OS-EGFP-NFAT2中α_(1A)-AR mRNA和蛋白的表达水平。③将U2OS-EGFP-NFAT2-α_(1A)-AR细胞接种于96孔板,分别加入NE(10^(-8)~10^(-5) mol·L^(-1))或α2-AR激动剂右美托咪定(DMED,10^^(-8.8)~10^(-5) mol·L^(-1))孵育30 min,通过高内涵筛选系统检测EGFP-NFAT2核转位。④将U2OS-EGFP-NFAT2-α_(1A)-AR细胞分为溶剂对照组、α1-AR拮抗剂萘派地尔(1μmol·L^(-1))组、NE(1μmol·L^(-1))组、萘派地尔+NE(各1μmol·L^(-1)共孵育)组、α2-AR拮抗剂阿替美唑(0.1μmol·L^(-1))组、DMED(0.1μmol·L^(-1))组、阿替美唑+DMED(各0.1μmol·L^(-1)共孵育)组和萘派地尔+DMED(萘派地尔1μmol·L^(-1)与DMED 0.1μmol·L^(-1)共孵育)组,药物孵育时间均为30 min,通过高内涵筛选系统检测EGFP-NFAT2核转位,验证该细胞α_(1A)-AR功能的特异性。结果①Hygro-B压力筛选得到58株U2OS-EGFP-NFAT2-α_(1A)-AR细胞,NE 10μmol·L^(-1)孵育后,其中50号细胞核内绿色荧光强度最强,故选定其为稳定共表达α_(1A)-AR和EGFPNFAT2的U2OS-EGFP-NFAT2-α_(1A)-AR细胞。②Western印迹法结果显示,U2OS-EGFP-NFAT2-α_(1A)-AR细胞可明显表达α_(1A)-AR蛋白,而对照细胞U2OS-EGFP-NFAT2中未见α_(1A)-AR蛋白表达。RT-qPCR结果显示,该细胞在传代5~20代内α_(1A)-AR mRNA均稳定表达,其表达水平为对照细胞的500~800倍。③NE或DMED使U2OS-EGFP-NFAT2-α_(1A)-AR细胞中EGFP-NFAT2核转位明显增加,半数有效浓度(EC50)分别为5.94×10^(-7)和6.15×10^(-8) mol·L^(-1)。④与溶剂对照组和萘派地尔组比较,NE组U2OS-EGFP-NFAT2-α_(1A)-AR细胞EGFP-NFAT2核转位明显增强(P<0.01),而萘派地尔+NE组EGFP-NFAT2核转位较NE组明显减弱(P<0.01)。与溶剂对照组和阿替美唑组比较,DMED组EGFP-NFAT2核转位明显增强(P<0.01),阿替美唑+DMED组EGFP-NFAT2核转位与DMED组比较无明显差别,而萘派地尔+DMED组EGFP-NFAT2核转位较DMED组明显减弱(P<0.01)。结论成功构建稳定共表达α_(1A)-AR和EGFP-NFAT2的U2OS-EGFPNFAT2-α_(1A)-AR细胞,可用于靶向α_(1A)-AR化合物筛选和受体分子机制研究。 展开更多
关键词 α1A-肾上腺素能受体 活化T细胞核因子2 核转位 去甲肾上腺素 高内涵筛选系统
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肾上腺素β受体基因、G蛋白基因和CYP2D6基因多态性对美托洛尔导致脂代谢异常的影响 被引量:2
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作者 刘泽 郝言 +1 位作者 张薇 徐辉 《中国医院用药评价与分析》 2023年第6期693-695,700,共4页
目的:研究肾上腺素β受体基因、G蛋白基因和CYP2D6基因多态性对美托洛尔导致脂代谢异常的影响。方法:选取2019年10月至2022年10月该院收治的初治高血压患者120例,检测β_(1)受体基因Ser49Gly、Gly389Arg多态;β_(2)受体基因Arg16Gly、Gl... 目的:研究肾上腺素β受体基因、G蛋白基因和CYP2D6基因多态性对美托洛尔导致脂代谢异常的影响。方法:选取2019年10月至2022年10月该院收治的初治高血压患者120例,检测β_(1)受体基因Ser49Gly、Gly389Arg多态;β_(2)受体基因Arg16Gly、Gln27Glu多态;β3受体基因Trp64Arg多态;代谢酶基因CYP2D6*10的P34S多态;G蛋白基因GNB3 C825T多态。比较美托洛尔单药治疗3个月后不同表型总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)和高密度脂蛋白(HDL)水平变化。结果:各基因位点不同基因型患者的年龄、性别、体重指数、基线TC和基线TG等指标比较,差异均无统计学意义(P>0.05)。治疗3个月后,β_(2)肾上腺素受体基因Arg16Gly患者的TG水平升高,其中Gly/Gly型患者升高幅度最高,Arg/Gly型次之,二者均高于Arg/Arg型,差异有统计学意义(P<0.05)。结论:β_(2)肾上腺素受体Arg16Gly多态与美托洛尔引起的血浆TG水平升高相关,携带2个G等位基因会导致服药后血脂水平明显升高。 展开更多
关键词 基因多态性 美托洛尔 血脂 三酰甘油 Β2肾上腺素受体
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太原市不同污染区域6~12岁儿童哮喘与β_(2) 肾上腺素能受体基因多态性的关系
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作者 王珏 王晓红 +4 位作者 李凌云 展磊 谭彩霞 李楠 马兰 《山西医科大学学报》 CAS 2023年第3期388-394,共7页
目的探讨太原市不同污染区儿童哮喘与β_(2)肾上腺素能受体基因多态性的关系。方法选取太原市3个不同空气质量地区的儿童,哮喘患儿共181例,150例健康儿童作为对照组。哮喘组儿童高污染区67例、中污染区61例,低污染区53例,对照组三区各5... 目的探讨太原市不同污染区儿童哮喘与β_(2)肾上腺素能受体基因多态性的关系。方法选取太原市3个不同空气质量地区的儿童,哮喘患儿共181例,150例健康儿童作为对照组。哮喘组儿童高污染区67例、中污染区61例,低污染区53例,对照组三区各50例。采用ELISA法测血清总IgE水平,提取血清中DNA,采用聚合酶链反应法(PCR)检测β_(2)肾上腺素能受体16、27位点基因多态性,即精氨酸(Arg)16甘氨酸(Gly)位点和谷氨酰胺(Gln)27谷氨酸(Glu)位点基因多态性,统计各基因型和等位基因频率。比较哮喘组与对照组血清总IgE水平的关系,比较哮喘组儿童不同污染区不同基因型血清总IgE水平的差异,同时比较不同污染区域各基因型频率和等位基因频率的分布。结果①哮喘组血清总IgE水平较对照组显著增高,差异有统计学意义(P<0.05),哮喘组儿童检测的β_(2)肾上腺素能受体16、27位点不同基因型之间血清总IgE水平差异无统计学意义。②哮喘组β_(2)肾上腺素能受体16位点基因型Arg/Arg频率较对照组均下降(P<0.05),哮喘组该基因型频率与空气污染程度呈负相关(t=-15.588,P<0.05);Gly/Gly频率哮喘组较对照组均升高(P<0.05),哮喘组该基因型频率与污染程度呈正相关(t=29.445,P<0.05)。③27位点基因型Gln/Glu、Glu/Glu频率哮喘组与对照组之间差异有统计学意义(P<0.05),高污染区哮喘组Gln/Glu基因型显著高于对照组(P<0.05),中、低污染区哮喘组Gln/Glu基因型显著低于对照组(P>0.05),高、中、低污染区哮喘组Glu/Glu基因型均显著高于对照组(P<0.05),但各基因型频率与污染程度均未见相关性(P>0.05)。结论不同空气质量下,哮喘患者血清总IgE水平与β_(2)肾上腺素能受体16、27基因多态性可能无关;不同空气质量下,哮喘可能与β_(2)肾上腺素能受体16位点基因表达有关,Gly/Gly基因型频率的增加会提高儿童哮喘的发病率;不同空气污染程度下哮喘患者发病率与27位点基因表达无关,所以推测空气污染可能未通过影响27位点基因表达而影响哮喘发病。 展开更多
关键词 哮喘 β_(2)肾上腺素能受体 基因多态性 儿童
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广西黑衣壮族ADRB2基因、IL-4R基因多态性与儿童哮喘发病的关联研究 被引量:1
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作者 马卓然 林娜 《右江医学》 2023年第6期512-518,共7页
目的探讨β2肾上腺素受体(ADRB2)基因rs1042713、白细胞介素4受体(IL-4R)基因rs1801275位点的多态性与儿童哮喘的相关性。方法采用临床病例对照法,选取黑衣壮中年龄<16岁的儿童200例。其中哮喘组100例,健康组100例。采用聚合酶连接... 目的探讨β2肾上腺素受体(ADRB2)基因rs1042713、白细胞介素4受体(IL-4R)基因rs1801275位点的多态性与儿童哮喘的相关性。方法采用临床病例对照法,选取黑衣壮中年龄<16岁的儿童200例。其中哮喘组100例,健康组100例。采用聚合酶连接酶链式反应(PCR-LCR chain reaction)检测ADRB2基因rs1042713、IL-4R基因rs1801275位点多态性,并分析其检测结果。结果(1)ADRB2基因rs1042713、IL-4R基因rs1801275位点均检测出AA、AG、GG三种基因型;(2)ADRB2基因rs1042713、IL-4R基因rs1801275位点基因型在哮喘组与健康组中差异有统计学意义(P<0.05);(3)ADRB2基因rs1042713位点基因型AA、AG+AA和等位基因A可能增加哮喘发病风险,GG+AG可降低哮喘发病风险。IL-4R基因rs1801275位点AG、AG+GG和等位基因G可降低哮喘发病风险,相较杂合子AG,纯合子AA+GG能增加哮喘发病风险。结论(1)广西黑衣壮儿童中存在ADRB2基因rs1042713、IL-4R基因rs1801275位点多态性;(2)ADRB2基因rs1042713、IL-4R基因rs1801275位点可能是广西黑衣壮儿童哮喘发病的相关因子。 展开更多
关键词 哮喘 β2肾上腺素受体基因 白细胞介素4受体基因 基因多态性 黑衣壮
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ADRB2, ADRB3, BDKRB2 and MTNR1B Genes Related to Body fat Modulation and ItsInteraction with Physical Activity and Blood Pressure
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作者 Aline Marcadenti 《Open Journal of Endocrine and Metabolic Diseases》 2015年第7期88-97,共10页
Hypertension (HTN) is the risk factor that most contributes to mortality rates in the world, followed by physical inactivity and obesity. Despite the influence of genetic factors on the genesis of HTN, blood pressure ... Hypertension (HTN) is the risk factor that most contributes to mortality rates in the world, followed by physical inactivity and obesity. Despite the influence of genetic factors on the genesis of HTN, blood pressure levels are strongly influenced by environmental factors such as physical inactivity and overweight, characterizing it as a polygenic disease. Genetic components and environmental factors such as physical exercise may modulate the phenotype of individuals predisposed to medical conditions such as HTN, independently of modifiable factors such as increased levels of adiposity;however, studies have shown that polymorphic forms detected in genes involved in the mechanisms of blood pressure regulation and also related to body fat modulation may interact with physical activity levels and HTN. The aim of this article is to review the interactions between polymorphisms in ADRB2, ADRB3, BDKRB2 and MTNR1B genes, physical activity and blood pressure. 展开更多
关键词 receptors adrenergic beta-2 receptor Bradykinin B Obesity Hypertension
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右美托咪定的中枢神经作用机制研究进展 被引量:2
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作者 宋一凡 江林昊 +1 位作者 杨谦梓 罗艳 《上海交通大学学报(医学版)》 CAS CSCD 北大核心 2024年第5期626-634,共9页
右美托咪定是一种α_(2)肾上腺素受体激动剂,具有镇静、镇痛、抗焦虑、抗交感神经的作用,目前已经成为临床麻醉和重症监护室广泛应用的药物。相比于麻醉科其他药物,右美托咪定没有明显的呼吸抑制作用且没有明显的血流动力学改变,且与其... 右美托咪定是一种α_(2)肾上腺素受体激动剂,具有镇静、镇痛、抗焦虑、抗交感神经的作用,目前已经成为临床麻醉和重症监护室广泛应用的药物。相比于麻醉科其他药物,右美托咪定没有明显的呼吸抑制作用且没有明显的血流动力学改变,且与其他麻醉药配伍可明显减少镇静镇痛药物的用量。在临床应用中发现,右美托咪定可以介导可唤醒的镇静效应。传统认为右美托咪定通过α_(2)肾上腺素受体发挥作用,可以发挥降低血压、舒张血管和降低心率的作用,但对于其如何影响脑内神经环路尚不清楚。近年来关于右美托咪定作用机制的研究逐渐增多,证实下丘脑腹外侧视前区(ventrolateral preoptic nucleus,VLPO)、蓝斑核(locus coeruleus,LC)、中脑腹侧被盖区(ventral tegmental area,VTA)等核团参与其介导的镇静作用,背根神经节(dorsal root ganglion,DRG)、颈上神经节(superior cervical ganglion,SCG)参与其介导的镇痛作用,下丘脑视前区(preoptic area,PO)和下丘脑室旁核(paraventricular nucleus,PVN)参与其介导的体温和水电解质平衡的变化,为理解右美托咪定在中枢神经系统的作用机制提供了新的方向。 展开更多
关键词 右美托咪定 α_(2)肾上腺素受体 镇静 镇痛 神经机制
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β_2肾上腺素受体基因多态性和支气管哮喘的关系 被引量:6
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作者 高金明 林耀广 +4 位作者 邱长春 高君 马毅 刘怡雯 刘英 《中国医学科学院学报》 CAS CSCD 北大核心 2002年第6期626-631,共6页
目的探讨β2肾上腺素受体(β2-adenergicreceptor,β2AR)基因多态性与我国北方汉族支气管哮喘遗传易感性及与哮喘临床表型间的关系。方法采用聚合酶链反应(PCR)—限制性内切酶片段长度多态性(RFLP)和等位基因特异性PCR(ASP)检测16、27、... 目的探讨β2肾上腺素受体(β2-adenergicreceptor,β2AR)基因多态性与我国北方汉族支气管哮喘遗传易感性及与哮喘临床表型间的关系。方法采用聚合酶链反应(PCR)—限制性内切酶片段长度多态性(RFLP)和等位基因特异性PCR(ASP)检测16、27、164位β2AR基因多态性在125名哮喘患者和96名健康对照者间的分布;并测定哮喘患者血清的TIgE、肺通气功能(FEV1,FEV1%,FEV1/FVC)、支气管舒张试验、乙酰甲胆碱(Mch)气道激发试验(如果FEV1%>70%)。结果Gly16纯合基因型在哮喘组的频率较健康对照组的频率明显升高(22.4%vs8.3%,P<0.05),优势比(OR)为2.918(95%CI:1.256~6.781);等位基因Gly16的频率在哮喘组明显高于健康对照组(0.26vs0.16,P<0.05);Gly16纯合子在夜间哮喘患者的频率分布较非夜间哮喘患者明显增高(35.3%vs13.5%,P<0.01);Gln27纯合子的个体较Glu27纯合子和Glu/Gln27的杂合子个体气道激发试验所用Mch剂量明显低犤(0.205±0.275)vs(2.11±3.00)vs(1.575±0.828)μmol,P<0.05犦;16,27位β2AR基因型对哮喘患者的气道可逆性的改善、总IgE水平、肺功能的损害无影响。结论Gly16/β2AR纯合基因型与我国北方汉族哮喘患者的遗传易感性有关,并与哮喘患者夜间症状加重明显有关,但不是哮喘发病的独立危险因素; 展开更多
关键词 Β2肾上腺素受体 基因多态性 支气管哮喘 夜间哮喘 聚合酶链反应 气道反应性
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中国汉族人中β_2肾上腺素能受体基因多态性与高血压病的关联性研究 被引量:16
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作者 朱建 江时森 +3 位作者 曹文 张启高 林欣 徐燕丰 《医学研究生学报》 CAS 2003年第2期123-126,共4页
目的 :调查 β2 肾上腺素能受体 (β2 AR) 16位和 2 7位基因多态性在中国汉族高血压病人群和正常血压人群中的分布频率 ,并分析β2 受体基因多态性和高血压病是否关联。 方法 :在我院近 2年住院患者中随机选取高血压病 2 19例 ,分为两... 目的 :调查 β2 肾上腺素能受体 (β2 AR) 16位和 2 7位基因多态性在中国汉族高血压病人群和正常血压人群中的分布频率 ,并分析β2 受体基因多态性和高血压病是否关联。 方法 :在我院近 2年住院患者中随机选取高血压病 2 19例 ,分为两组 ,发病年龄 <6 0岁者为H1组 ,>6 0岁者为H2组 ;正常血压者 78例 ,也分为两组 ,年龄≥ 4 0岁者为N1组 ,<4 0岁者为N2组。从外周血抽提DNA ,进行聚合酶链反应 (PCR) ,取PCR产物分别用限制性内切酶NcoⅠ和BbvⅠ酶切 ,确定基因型。 结果 :高血压病组 (H组 )中 ,β2 AR 16位点基因型分布与正常血压组 (N组 )比无显著差异 ;而 2 7位点基因型与N组比较 ,比数比 (OR)为 2 .35 ,95 %可信限 (CI)为 1.34~ 4 .15 ,有极显著差异(P <0 .0 1)。等位基因频率也有极显著性差异 (P <0 .0 1)。 结论 :我国汉族人群中 β2 AR基因 2 展开更多
关键词 高血压病 Β2肾上腺素能受体 基因多态性
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