The changes of beta-adrenergic receptors (AARs) in lung tissue in endotoxin-induced acute lung injury was investigated with radioligand bindig assay in rats. The lipid fluidity and phospholipid content of the cellular...The changes of beta-adrenergic receptors (AARs) in lung tissue in endotoxin-induced acute lung injury was investigated with radioligand bindig assay in rats. The lipid fluidity and phospholipid content of the cellular membrane of lung tissue were measured with fluorescent polarization and high performance liquid chromatography respectively. The findings were as follows:1- Four hours after endotoxin injection, there was a 47% decrease of the maximal binding capacity of fyARsas compared with the control.2. Endotoxin was able to decrease the lipid fluidity and phospholipid content of the pulmonary cellular membrane markedly and at the same time. There was an elevated activity of phospholipase A2 in the pulmonary tissueThese findings suggest that the decrease of the binding capacity of &ARs results in a decrease of the PAR mediated functions, which plays a ro1e in the pathogensis of endotoxin-induced acute lung injury and the activation of phospholipase A2 which is an important factor to reduce the phospholipid content of cell membrane and subsequently to decrease its lipid fluidity, can result in a reduction of the lateral diffusion and rotatory movement of β-ARs and to decrease the chances of β-ARs to bind with the ligands.展开更多
BACKGROUND： The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is he...BACKGROUND： The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is helpful to develop researches on the genetics of various diseases including hypertension in Mongolian population. OBJECTIVE： To analyze the association between the polymorphism of beta1 adrenergic receptor （β1-AR） gene G1165C （Arg389Gly）, an important candidate gene for various diseases of cardiovascular system, and essential hypertension in Mongolian population. DESIGN ： A cross-sectional study SETTINGS： Department of Neurology, the First Affiliated Hospital of Inner Mongolia Medical College; Wulate Houqi Red Cross Society. PARTICIPANTS： The survey was carried out from February 2003 to March 2005. Totally 239 Mongolian residents, whose blood relations of 3 generations were all Mongolians, were selected from Wulate Houqi, Inner Mongolia, and they were all informed with the survey and detected items. Based on the diagnostic standard of hypertension set by WHO in 1999, the subjects were divided into two groups according to the level blood pressure： ① Normal blood pressure group （n=117）： systolic blood pressure （SBP） 〈 140 mm Hg （1 mm Hg =0.133 kPa）, diastolic blood pressure （DBP） 〈 90 mm Hg, and those having histories of cerebrovascular disease, heart disease, diseases of liver, kidney and tiroides, and diabetes mellitus were excluded. ② Essential hypertension group （n=122）： including 51 patients with simple high SBP. All the enrolled subjects had no blood relationship with each other, and had no history of miscegenation. METHODS ： The body height, body mass, waist circumference and blood lipids were measured routinely, and their habits of smoking and drinking were also investigated. Penpheral venous blood （5 mL） was drawn, the genome DNA was extracted, and the polymorphisms of the β1-AR Gl165C （Gly389Arg） genotype were detected with the Sequenom system. Polymerase chain reaction （PCR） experiment and SNP detection were performed in Huada Gene Laboratory of Bejing, then the univariate analysis of variance was applied in the sample comparison among groups, and the chi-square test was used to compare the genotypes and allele frequencies. The odd ratio （OR） and 95% confidence interval （CO were calculated. MAIN OUTCOME MEASURES： The distributions of β1-AR Gl165C （Gly389Arg） genotypes and alleles were observed. RESULTS： A11 the 239 subjects were involved in the analysis of results, and no one missed, ①Comparison of β1-AR G1165C （Gly389Arg） genotypes and allele distnbutions： In Mongolian population, the frequencies of CC and GG＋GC genotypes at β1-AR G1165C （Gly389Arg） site in the essential hypertension group （72%, 28%） were not significantly different from those in the normal blood pressure group （67%, 33%） （xz=0.841, P=-0.359; OR 0.773, 95%Cl： 0.445-1.342）; The frequencies of C and G alleles also had no significant differences between the essential hypertension group （85%, 15%） and the normal blood pressure group （82%, 18%） （x^2=1.136, P=-0.287; OR： 0.769, 95%Cl： 0.747-1.248）. ②The frequencies of CC and GG＋GC genotypes at β1-AR G1165C （Gly389Arg） site had no significant differences between the patients with simple high SBP （71%, 29%） and the normal blood pressure group （x^2=0.250, P=-0.617; OR： 0.833, 95%C/： 0.408-1.703）; The frequencies of C and G alleles were not significantly different between the patients with simple high SBP （86%, 14%） and the normal blood pressure group （x^2=0.670, P=-0.413; OR 0.766, 95%Cl： 0.404-1.453）. CONCLUSION： In Mongolian population, the distributions of the genotypes and alleles of β1-AR Gl165C （Gly389Arg） have no obvious differences between the subjects with normal blood pressure and the patients with essential hypertension （including simple SBP increase）, which suggests that G1165C （Glu389Asp） site of β1-AR gene may be not a genetic mark of essential hypertension and simple high SBP in Mongolian population.展开更多
Beta-adrenergic receptors in the brain are involved in modulating cerebral blood flow (CBF) and cerebral energy metabolism (CEM). Because of the difficult availability of brain tissue samples, investigation of the rel...Beta-adrenergic receptors in the brain are involved in modulating cerebral blood flow (CBF) and cerebral energy metabolism (CEM). Because of the difficult availability of brain tissue samples, investigation of the relevant beta-receptor of brain is limited. In the present study, the density of beta-receptors in brain tissues and in circulating lymphocytes was measured by the method of radio-ligand receptor binding (RLBA), in brain injury or brain tumor and a correlation analysis was performed. Our results show that there is linear correlation between the beta-receptors in brain tissue and in peripheral blood lymphocytes (r= 0. 811 , P<0. 01) in cases of increased permeability of bloodbrain barrier during brain injury or brain tumor.展开更多
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
Summary: The experimental results showed that the level of CAMP, the ratio of cAPM to cGMP, IL-2R expression and IL-2 production in vitro in lymphocytes immediate and 2 weeks after car- diopulmonary bypass (CPB) were ...Summary: The experimental results showed that the level of CAMP, the ratio of cAPM to cGMP, IL-2R expression and IL-2 production in vitro in lymphocytes immediate and 2 weeks after car- diopulmonary bypass (CPB) were significantly lower than those before anesthetics in the patients undergoing cardiac surgery with CPB. These findings suggested that CPB could cause serious damage to adrenergic beta receptor-adenylate cyclase system on circulating lymphocytes surfaces, which might be one of the mechanisms resulting in immunosuppression after open heart surgery with CPB.展开更多
In this paper, the distribution of pulmonary beta-adrenergic receptors (beta-receptors) innormal and experimental allergic asthmatic guinea pigs was determined using autoradiograph-ic method. The results showed that t...In this paper, the distribution of pulmonary beta-adrenergic receptors (beta-receptors) innormal and experimental allergic asthmatic guinea pigs was determined using autoradiograph-ic method. The results showed that the distribution of beta-receptors in the lung sections waswidespread. There was a significant decrease of beta-receptor density in several tissue struc-tures of asthmatic guinea pig lungs compared with the controls, a 23.73% decrease in beta-recep-tor binding sites in bronchiolar smooth muscles and a 18.65% decrease in bronchial smoothmuscles; a 23 .53%. a 14.23% and a 17. 16% decrease in bronchiolar epithelium, in bronchialepithelium and in alveolar epithelium respectively. The results indicated that the beta-recep-tor decrease in smooth muscles in experimental asthmatic guinea pig lungs might be one ofthe important factors which made the tension of smooth muscles increase. The relationshipbetween the beta-receptor decrease of other sites and bronchial asthma needs to be studiedfurther.展开更多
To study the changes in every part of the β-adrenergic signal transduction pathway and their effects on ischemic preconditioning of rat myocardium in vivo. SD rats were divided into three groups： IP group, I/R group...To study the changes in every part of the β-adrenergic signal transduction pathway and their effects on ischemic preconditioning of rat myocardium in vivo. SD rats were divided into three groups： IP group, I/R group and CON group. The IP group was further divided into PC1-, 2-, 3-, and PC1＋, 2＋, 3＋ groups according to preconditioning procedure. The rats received surgical procedure and underwent left coronary artery occlusion and reperfusion. We analyzed the infarct size by TTC staining, measured serum myocardial enzymes, studied the β-AR Bmax and Kd by radioligand binding assay of receptors, checked the activity of AC and PKA by the method of biochemistry and examined the content of cAMP by radioimmunoassay. The infarct area was much smaller in the IP group than in the I/R group （P〈0. 001）, while the enzymes were significantly higher in I/R （P〈0. 001）. The Bmax of β-AR in IP was much higher than that in I/R （P〈0. 001）, but no difference in Kd could be seen between IP and I/R groups. In IP, the activity of AC and PKA and the content of cAMP were higher than those in I/R （P〈0.05, 0. 002 and 0. 001, respectively）. In the procedure of preconditioning, the content of cAMP and the activity of PKA showed the characteristic of cyclic fluctuation. Ischemic preconditioning can protect the heart from necrosis and reduce endo-enzyme leakage. The system of β-adrenergic signal transduction pathway probably takes part in the protection effect of the IP, which might be elicited by the PKA .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
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
One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between...One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors.Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse models.Moreover,there is a direct relationship between pIgR expression and transaminase levels in patients with AIH.In this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH.Reg3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota disruption.Conversely,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis.RNA sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through pIgR.Furthermore,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in AIH.Through this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.展开更多
Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In...Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease.展开更多
文摘The changes of beta-adrenergic receptors (AARs) in lung tissue in endotoxin-induced acute lung injury was investigated with radioligand bindig assay in rats. The lipid fluidity and phospholipid content of the cellular membrane of lung tissue were measured with fluorescent polarization and high performance liquid chromatography respectively. The findings were as follows:1- Four hours after endotoxin injection, there was a 47% decrease of the maximal binding capacity of fyARsas compared with the control.2. Endotoxin was able to decrease the lipid fluidity and phospholipid content of the pulmonary cellular membrane markedly and at the same time. There was an elevated activity of phospholipase A2 in the pulmonary tissueThese findings suggest that the decrease of the binding capacity of &ARs results in a decrease of the PAR mediated functions, which plays a ro1e in the pathogensis of endotoxin-induced acute lung injury and the activation of phospholipase A2 which is an important factor to reduce the phospholipid content of cell membrane and subsequently to decrease its lipid fluidity, can result in a reduction of the lateral diffusion and rotatory movement of β-ARs and to decrease the chances of β-ARs to bind with the ligands.
基金a grant from theGreat Program of Inner Mongo-lia Medical College, No.NY2004ZD006
文摘BACKGROUND： The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is helpful to develop researches on the genetics of various diseases including hypertension in Mongolian population. OBJECTIVE： To analyze the association between the polymorphism of beta1 adrenergic receptor （β1-AR） gene G1165C （Arg389Gly）, an important candidate gene for various diseases of cardiovascular system, and essential hypertension in Mongolian population. DESIGN ： A cross-sectional study SETTINGS： Department of Neurology, the First Affiliated Hospital of Inner Mongolia Medical College; Wulate Houqi Red Cross Society. PARTICIPANTS： The survey was carried out from February 2003 to March 2005. Totally 239 Mongolian residents, whose blood relations of 3 generations were all Mongolians, were selected from Wulate Houqi, Inner Mongolia, and they were all informed with the survey and detected items. Based on the diagnostic standard of hypertension set by WHO in 1999, the subjects were divided into two groups according to the level blood pressure： ① Normal blood pressure group （n=117）： systolic blood pressure （SBP） 〈 140 mm Hg （1 mm Hg =0.133 kPa）, diastolic blood pressure （DBP） 〈 90 mm Hg, and those having histories of cerebrovascular disease, heart disease, diseases of liver, kidney and tiroides, and diabetes mellitus were excluded. ② Essential hypertension group （n=122）： including 51 patients with simple high SBP. All the enrolled subjects had no blood relationship with each other, and had no history of miscegenation. METHODS ： The body height, body mass, waist circumference and blood lipids were measured routinely, and their habits of smoking and drinking were also investigated. Penpheral venous blood （5 mL） was drawn, the genome DNA was extracted, and the polymorphisms of the β1-AR Gl165C （Gly389Arg） genotype were detected with the Sequenom system. Polymerase chain reaction （PCR） experiment and SNP detection were performed in Huada Gene Laboratory of Bejing, then the univariate analysis of variance was applied in the sample comparison among groups, and the chi-square test was used to compare the genotypes and allele frequencies. The odd ratio （OR） and 95% confidence interval （CO were calculated. MAIN OUTCOME MEASURES： The distributions of β1-AR Gl165C （Gly389Arg） genotypes and alleles were observed. RESULTS： A11 the 239 subjects were involved in the analysis of results, and no one missed, ①Comparison of β1-AR G1165C （Gly389Arg） genotypes and allele distnbutions： In Mongolian population, the frequencies of CC and GG＋GC genotypes at β1-AR G1165C （Gly389Arg） site in the essential hypertension group （72%, 28%） were not significantly different from those in the normal blood pressure group （67%, 33%） （xz=0.841, P=-0.359; OR 0.773, 95%Cl： 0.445-1.342）; The frequencies of C and G alleles also had no significant differences between the essential hypertension group （85%, 15%） and the normal blood pressure group （82%, 18%） （x^2=1.136, P=-0.287; OR： 0.769, 95%Cl： 0.747-1.248）. ②The frequencies of CC and GG＋GC genotypes at β1-AR G1165C （Gly389Arg） site had no significant differences between the patients with simple high SBP （71%, 29%） and the normal blood pressure group （x^2=0.250, P=-0.617; OR： 0.833, 95%C/： 0.408-1.703）; The frequencies of C and G alleles were not significantly different between the patients with simple high SBP （86%, 14%） and the normal blood pressure group （x^2=0.670, P=-0.413; OR 0.766, 95%Cl： 0.404-1.453）. CONCLUSION： In Mongolian population, the distributions of the genotypes and alleles of β1-AR Gl165C （Gly389Arg） have no obvious differences between the subjects with normal blood pressure and the patients with essential hypertension （including simple SBP increase）, which suggests that G1165C （Glu389Asp） site of β1-AR gene may be not a genetic mark of essential hypertension and simple high SBP in Mongolian population.
文摘Beta-adrenergic receptors in the brain are involved in modulating cerebral blood flow (CBF) and cerebral energy metabolism (CEM). Because of the difficult availability of brain tissue samples, investigation of the relevant beta-receptor of brain is limited. In the present study, the density of beta-receptors in brain tissues and in circulating lymphocytes was measured by the method of radio-ligand receptor binding (RLBA), in brain injury or brain tumor and a correlation analysis was performed. Our results show that there is linear correlation between the beta-receptors in brain tissue and in peripheral blood lymphocytes (r= 0. 811 , P<0. 01) in cases of increased permeability of bloodbrain barrier during brain injury or brain tumor.
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.
文摘Summary: The experimental results showed that the level of CAMP, the ratio of cAPM to cGMP, IL-2R expression and IL-2 production in vitro in lymphocytes immediate and 2 weeks after car- diopulmonary bypass (CPB) were significantly lower than those before anesthetics in the patients undergoing cardiac surgery with CPB. These findings suggested that CPB could cause serious damage to adrenergic beta receptor-adenylate cyclase system on circulating lymphocytes surfaces, which might be one of the mechanisms resulting in immunosuppression after open heart surgery with CPB.
文摘In this paper, the distribution of pulmonary beta-adrenergic receptors (beta-receptors) innormal and experimental allergic asthmatic guinea pigs was determined using autoradiograph-ic method. The results showed that the distribution of beta-receptors in the lung sections waswidespread. There was a significant decrease of beta-receptor density in several tissue struc-tures of asthmatic guinea pig lungs compared with the controls, a 23.73% decrease in beta-recep-tor binding sites in bronchiolar smooth muscles and a 18.65% decrease in bronchial smoothmuscles; a 23 .53%. a 14.23% and a 17. 16% decrease in bronchiolar epithelium, in bronchialepithelium and in alveolar epithelium respectively. The results indicated that the beta-recep-tor decrease in smooth muscles in experimental asthmatic guinea pig lungs might be one ofthe important factors which made the tension of smooth muscles increase. The relationshipbetween the beta-receptor decrease of other sites and bronchial asthma needs to be studiedfurther.
文摘To study the changes in every part of the β-adrenergic signal transduction pathway and their effects on ischemic preconditioning of rat myocardium in vivo. SD rats were divided into three groups： IP group, I/R group and CON group. The IP group was further divided into PC1-, 2-, 3-, and PC1＋, 2＋, 3＋ groups according to preconditioning procedure. The rats received surgical procedure and underwent left coronary artery occlusion and reperfusion. We analyzed the infarct size by TTC staining, measured serum myocardial enzymes, studied the β-AR Bmax and Kd by radioligand binding assay of receptors, checked the activity of AC and PKA by the method of biochemistry and examined the content of cAMP by radioimmunoassay. The infarct area was much smaller in the IP group than in the I/R group （P〈0. 001）, while the enzymes were significantly higher in I/R （P〈0. 001）. The Bmax of β-AR in IP was much higher than that in I/R （P〈0. 001）, but no difference in Kd could be seen between IP and I/R groups. In IP, the activity of AC and PKA and the content of cAMP were higher than those in I/R （P〈0.05, 0. 002 and 0. 001, respectively）. In the procedure of preconditioning, the content of cAMP and the activity of PKA showed the characteristic of cyclic fluctuation. Ischemic preconditioning can protect the heart from necrosis and reduce endo-enzyme leakage. The system of β-adrenergic signal transduction pathway probably takes part in the protection effect of the IP, which might be elicited by the PKA .
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.
基金Supported by the National Natural Science Foundation of China(No.30672730)the Research Project of Hubei Provincial Science and Technology Department(No.2006AA301C24)the Fundamental Research Funds for the Central Universities,Huazhong University of Science and Technology(No. 2010JC058)
文摘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.
基金supported by the National Natural Science Foundation of China(82070593)the Zhejiang Provincial Natural Science Foundation(LD21H030002)+1 种基金the Department of Science and Technology of Zhejiang Province(ZY2019008)the Youth Program of the National Natural Science Foundation of China(82200632).
文摘One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors.Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse models.Moreover,there is a direct relationship between pIgR expression and transaminase levels in patients with AIH.In this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH.Reg3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota disruption.Conversely,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis.RNA sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through pIgR.Furthermore,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in AIH.Through this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.
基金supported by the Notional Natural Science Foundation of China,Nos.81371213 and 8107098 7the Natural Science Foundation of Shanghai,No.21ZR1468400 (all to QLY)。
文摘Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease.
