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
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
Adrenergic receptor dysfunction is suggested as a potential cause of hippocampal vulnerability to stress-related pathology. We examined mRNA expression of adrenergic receptor （AR） subtypes α1-AR, α1-AR, and β1-AR...Adrenergic receptor dysfunction is suggested as a potential cause of hippocampal vulnerability to stress-related pathology. We examined mRNA expression of adrenergic receptor （AR） subtypes α1-AR, α1-AR, and β1-AR in hippocampal subregions （CA1, CA3, dentate gyrus） using in situ hybridization in a depression model induced by chronic unpredictable mild stress and social isolation, α1-AR mRNA expression was significantly increased in the CA3 and dentate gyrus, β1-AR mRNA was significantly increased in the CA1, and α1-AR mRNA remained unchanged in all regions of depression rats compared with controls. Thus, different AR subtypes exhibit a differing pattern of mRNA expression in various hippocampal subregions following depression.展开更多
目的检测不同原发疾病所致心衰患者血清中的β_3肾上腺素受体自身抗体(β_3-AAB)的类别,并分析其可能的医学意义。方法以合成的β_3肾上腺素受体细胞外第二环肽段作为抗原,应用酶联免疫吸附实验,检测临床甄选的160例扩心病、冠心病、高...目的检测不同原发疾病所致心衰患者血清中的β_3肾上腺素受体自身抗体(β_3-AAB)的类别,并分析其可能的医学意义。方法以合成的β_3肾上腺素受体细胞外第二环肽段作为抗原,应用酶联免疫吸附实验,检测临床甄选的160例扩心病、冠心病、高心病和风心病所致心衰病患者及100例健康正常对照者血清中IgG和IgM类β_3-AAB的阳性率及抗体水平,并分析它们对患者心功能的影响。结果部分心衰患者和正常对照血清中存在Igc和/或IgM类β_3-AAB。扩心病所致心衰患者血清中,IgG类β_3-AAB的阳性率和抗体水平均显著高于正常对照(40.0% vs 8.0%,P<0.01和1.18±0.29 vs 0.92±0.20,P<0.05);IgM类β_3-AAB阳性率也显著高于正常人(53.3% vs 12.0%,P<0.01),但其抗体水平与正常对照相比差异无统计学意义(0.52±0.08 vs 0.52±0.09,P>0.05)。冠心病所致心衰患者血清中,IgG类β_3-AAB阳性率也显著高于正常人(25.6% vs 8.0%,P<0.01),但其抗体水平与正常对照相比差异无统计学意义(1.02±0.17 vs 0.92±0.20,P>0.05)。而高心病和风心病所致心衰患者血清中,IgG类β_3-AAB的阳性率(20.0%和30.0%)和抗体水平(0.96±0.11和0.96±0.19)以及IsM类β_3- AAB的阳性率(16.7%和20.0%)和抗体水平(0.51±0.05和0.48±0.04)与相应正常对照比较,差异无统计学意义(P>0.05)。正常对照Igc类β_3-AAB水平明显高于IgM类(0.92±0.20 vs 0.52±0.09,P<0.01),各心衰组有相同的规律。IgG类β_3-AAB对心衰患者左室射血分数有显著影响(F=6.178,P=0.014),进一步分析发现,扩心病患者Igc类β_3-AAB阳性者心脏左室射血分数明显高于阴性者(25.1±2.9 vs 15.5±1.6,P<0.01)。结论IgG类β_3-AAB可能是重要的功能性抗体,主要参与扩心病患者心衰的病理生理过程。展开更多
基金This study was supported by the National Natural Science Foundation of China (30371223)the Major State Basic Research Development Program of China (2001CB510310).
文摘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.
基金supported by the Key Laboratory of Brain Disease Bioinformation of Jiangsu Province of China,No.Jsbl1202
文摘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.
基金Opening Projects from Laboratory of Acupuncture-Medicine, Nanjing University of Chinese Medicine, No. KJA200505, KJA200803Doctor Station Foundation of the Ministry of Education, No. 2009323711009the National Natural Science Foundation of China, No. 30901923
文摘Adrenergic receptor dysfunction is suggested as a potential cause of hippocampal vulnerability to stress-related pathology. We examined mRNA expression of adrenergic receptor （AR） subtypes α1-AR, α1-AR, and β1-AR in hippocampal subregions （CA1, CA3, dentate gyrus） using in situ hybridization in a depression model induced by chronic unpredictable mild stress and social isolation, α1-AR mRNA expression was significantly increased in the CA3 and dentate gyrus, β1-AR mRNA was significantly increased in the CA1, and α1-AR mRNA remained unchanged in all regions of depression rats compared with controls. Thus, different AR subtypes exhibit a differing pattern of mRNA expression in various hippocampal subregions following depression.
文摘目的检测不同原发疾病所致心衰患者血清中的β_3肾上腺素受体自身抗体(β_3-AAB)的类别,并分析其可能的医学意义。方法以合成的β_3肾上腺素受体细胞外第二环肽段作为抗原,应用酶联免疫吸附实验,检测临床甄选的160例扩心病、冠心病、高心病和风心病所致心衰病患者及100例健康正常对照者血清中IgG和IgM类β_3-AAB的阳性率及抗体水平,并分析它们对患者心功能的影响。结果部分心衰患者和正常对照血清中存在Igc和/或IgM类β_3-AAB。扩心病所致心衰患者血清中,IgG类β_3-AAB的阳性率和抗体水平均显著高于正常对照(40.0% vs 8.0%,P<0.01和1.18±0.29 vs 0.92±0.20,P<0.05);IgM类β_3-AAB阳性率也显著高于正常人(53.3% vs 12.0%,P<0.01),但其抗体水平与正常对照相比差异无统计学意义(0.52±0.08 vs 0.52±0.09,P>0.05)。冠心病所致心衰患者血清中,IgG类β_3-AAB阳性率也显著高于正常人(25.6% vs 8.0%,P<0.01),但其抗体水平与正常对照相比差异无统计学意义(1.02±0.17 vs 0.92±0.20,P>0.05)。而高心病和风心病所致心衰患者血清中,IgG类β_3-AAB的阳性率(20.0%和30.0%)和抗体水平(0.96±0.11和0.96±0.19)以及IsM类β_3- AAB的阳性率(16.7%和20.0%)和抗体水平(0.51±0.05和0.48±0.04)与相应正常对照比较,差异无统计学意义(P>0.05)。正常对照Igc类β_3-AAB水平明显高于IgM类(0.92±0.20 vs 0.52±0.09,P<0.01),各心衰组有相同的规律。IgG类β_3-AAB对心衰患者左室射血分数有显著影响(F=6.178,P=0.014),进一步分析发现,扩心病患者Igc类β_3-AAB阳性者心脏左室射血分数明显高于阴性者(25.1±2.9 vs 15.5±1.6,P<0.01)。结论IgG类β_3-AAB可能是重要的功能性抗体,主要参与扩心病患者心衰的病理生理过程。
基金supported by the National Natural Science Foundation of China Grants(81202596)Specialized Research Fund for the Doctoral Program of Higher Education(20113420120006)+1 种基金Grants for Scientific Research of BSKY(XJ201021) from Anhui Medical University,Research Foundation of Anhui Medical University(2011xkj011)Anhui province Nature Science Foundation in University(KJ2012Z158)
