肾上腺素能β受体在去甲肾上腺素引起的心肌细胞离子泵损害中的作用研究

本文报告以去甲肾上腺素(NE)50μg/kg由家兔耳静脉注射,2分钟后致死。取左心室肌制备膜微粒体,测Na~+/K~+-ATP酶及Ca~(2+)-ATP酶活性,过氧化脂质(LPO)含量;取心尖部肌肉匀浆后提取及测定cAMP含量。结果,NE明显抑制二酶活性,P均<0.001,明显增加LPO及cAMP含量,P均<0.001。在注射NE前2分钟自耳静脉注射α受体阻滞剂酚妥拉明1mg/kg,或β受体阻滞剂心得静60μg/kg,或二者合用。结果示β受体阻滞剂明显阻抑NE效应,P<0.001或0.05;而α受体阻滞剂未显示阻抑作用,P均>0.05。结果提示,β受体在介导NE效应中占优势。     

β肾上腺素能受体在梗死后心脏重构中作用的研究进展

心肌梗死后心脏重构涉及多种信号传导,与心力衰竭、心律失常密切相关.β肾上腺素能受体(β-AR)参与凋亡、炎症、纤维化、心肌肥大等病理过程,在梗死后心脏重构中发挥关键的调节作用.3种β-AR在梗死后重构中介导了不同的信号调节过程,交感神经持续过度刺激通过β1-AR促进不良重构,而β2-AR和β3-AR则发挥保护作用.深入...     

β3肾上腺素受体在心血管系统中的作用

β3受体属于G蛋白耦联受体超家族成员,除了存在于脂肪组织外,最近药理学、分子学研究证实,β3受体也存在于心血管组织中,且其功能性的表达介导心肌的负性变力效应和血管舒张作用.为进一步探讨心力衰竭的病理生理机制提供了理论依据,也为β受体阻滞剂治疗心力衰竭提供了新的靶点.     

β2肾上腺素能受体基因多态性与原发性高血压的相关性研究

目的:检测贵州汉族人群β2 肾上腺素能受体基因Gln27Glu多态性,并探讨其与贵州汉族人群原发性高血压(EH)以及其他心血管病危险因素的关系。方法:选择131例EH患者及40例正常人为对象,通过聚合酶链反应确定基因型,并测定每个对象的体质指数(BMI)、腰围、臀围、腰围/臀围、空腹血三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL- C)、高密度脂蛋白胆固醇(HDL- C)以及LP(α)等。结果:①Gln27Glu多态性的基因型频率和等位基因频率在EH组和对照组间差异无统计学意义 (P>0.05),但 Glu27/Glu、Gln27/Glu基因型频率和Glu27等位基因频率在3级EH组的比例明显高于其在对照组及 1、2 级 EH组的比例(P<0.05);②Glu27/Glu、Gln27/Glu两种基因型个体的TC显著高于 Gln27/Gln基因型个体 (P<0.05),而 BMI、腰围/臀围、TG、LDL- C、HDL- C以及LP(α)等在三种基因型之间差异无统计学意义(P>0.05)。结论:Gln27Glu基因多态性与3级EH及TC有关联。     

β3肾上腺素能受体与心血管疾病

β3 肾上腺素能受体是新近发现的,继β1 和β2 之后的第 3个β型肾上腺素能受体亚型。近年来国内外的研究表明:该受体基因突变或基因多态性与机体肥胖及心血管疾病相关;心力衰竭时该受体的含量明显增加,应用该受体激动剂后可明显加重心力衰竭,增加病死率。β3 肾上腺素能受体与心血管疾病的相关研究可能为心血管疾病的预测、防治开发一种新思路。     

β3肾上腺素能受体基因多态性与原发性高血压相关性研究现状

原发性高血压(EH)常伴随着代谢方面的异常,如肥胖、体重增加、胰岛素抵抗(IR)、糖尿病(DM)等,这些均被证实与β3肾上腺素能受体(β3-AR)基因的多态性有关。β3-AR是交感神经系统的重要组成部分,它主要介导脂肪分解与热生成作用,该受体激动时局部脂肪分解增加。如果决定β3-AR性     

基因转染β肾上腺素能受体激酶抑制剂对支气管哮喘小鼠β2肾上腺素能受体和环腺苷酸的影响

目的　研究基因转染β肾上腺素能受体激酶抑制剂 (βARKct)对应用 β2 肾上腺素能受体 (β2 AR)激动剂后支气管哮喘 (简称哮喘 )小鼠肺部 β2 AR和环腺苷酸 (cAMP)的作用 ,并探讨不同基因转染途径对两者的影响。方法　 (1)以 10 %卵清蛋白致敏并激发BALB/c小鼠建立哮喘模型 ,并设正常小鼠为正常对照组 (A组 )。将哮喘小鼠分为 7组 ,每组 5只 ,分别给予生理盐水 (哮喘对照组 ,B组 )肌肉注射、沙丁胺醇肌肉注射 (C、D、E、F、G组 ) ,以建立长期应用 β2 AR激动剂的哮喘动物模型。(2 )构建带有 βARKct基因表达质粒 ,通过小鼠尾静脉注射和气管内滴入的转染途径进行基因转染。D组给予静脉注射转染 βARKct、E组给予静脉注射转染空载质粒、F组给予气管滴注转染 βARKct、G组给予气管滴注转染空载质粒。(3)用Western blot检测基因的表达。放射免疫法检测小鼠肺部的 β2 AR和cAMP的水平。结果　 (1)基因转染 βARKct在小鼠肺部有表达 ,且F组的基因表达量高于D组。(2 )A组 β2 AR和cAMP分别为 (10 9± 11)fmol/mg、(3 5 0± 0 5 0 )pmol/L ;B组 β2 AR和cAMP分别为 (81± 3)fmol/mg、(1 5 0± 0 2 0 )pmol/L ,与A组比较差异有显著性 (P均 <0 0 5 ) ;C组 β2 AR和cAMP分别为(6 3± 3)fmol/mg、(0 90± 0 10     

老年人膀胱逼尿肌β受体反应性环腺苷酸水平变化及其调节机制

目的　探讨年龄对人膀胱逼尿肌肾上腺素能 β受体反应性环腺苷酸 (cAMP)水平的影响及受体后信号传递途径调节因素的作用。　方法　用放射免疫法检测在异丙肾上腺素、BRL 37344和forskolin作用下 ,老年组 (15例 )和青年组 (7例 )逼尿肌组织中cAMP含量以及百日咳毒素 (PTX)、霍乱毒素 (CTX)、vinpocetine和KT 5 72 0对其影响。　结果　在异丙肾上腺素、BRL 37344和forskolin存在下老年组逼尿肌组织cAMP含量分别为 (15 0± 1 6 )、(12 2± 1 8)pmol mg蛋白和 (5 4 5± 4 0 )pmol mg蛋白 ,青年组显著下降 (P <0 0 1) ;CTX对老年组cAMP水平无显著影响 ,PTX与KT 5 72 0显著提高了 β受体激动剂存在下的cAMP含量 ,对forskolin的作用无明显影响 ,vinpocetine能显著提高 β受体激动剂和forskolin作用后的cAMP水平。　结论　老年人膀胱逼尿肌的 β受体反应性cAMP水平显著下降 ,腺苷酸环化酶活性的下降和抑制性G蛋白Gi的活性提高可能是其生化基础 ;Ⅰ型磷酸二酯酶和蛋白激酶A抑制剂能改善老年人逼尿肌的 β受体反应性 ,可以用于治疗老年人膀胱储尿功能障碍。     

β3肾上腺素能受体与心力衰竭的研究进展

β3肾上腺素能受体(β3AR)属于G蛋白偶联受体超家族,研究显示,与β1AR和β2AR不同,β3AR激动可抑制心肌收缩力。心力衰竭时左室β3AR密度增高,心肌细胞β3AR mRNA及受体蛋白表达上调。β3AR与Gi/o蛋白偶联,参与NO-cGMP介导的负性肌力作用。β1／β2／β3AR阻滞剂布拉洛尔可以完全阻断其作用,而β1／β2AR阻滞剂无效。心力衰竭时随交感神经持续激活,出现β1AR下调、β2AR功能性脱偶联、β3AR持续上调,导致心功能的进展性恶化。本文拟对β3AR与充血性心力衰竭的研究进展作一综述。     

瘦素对大鼠气道平滑肌β_2肾上腺素能受体表达的影响

目的观察瘦素(LP)对大鼠气道平滑肌细胞β2肾上腺素能受体(β2-AR)表达的影响,探讨LP参与哮喘发病的机制。方法组织贴块法原代培养大鼠气道平滑肌细胞(ASMCs),随机分为空白对照组(A组),LP 50 ng/L组(B组),LP 100 ng/L组(C组),LP 200 ng/L组(D组)及LP拮抗剂组(LP 200 ng/L+LP拮抗剂200 ng/L)(E组)分别干预24 h,采用Western印迹法及实时荧光半定量RT-PCR测瘦素受体(Ob-R)及β2-AR的表达。结果与A组相比,B、C、D组Ob-R表达明显升高,而β2-AR表达下降,证实LP可以上调Ob-R的表达并抑制β2-AR的表达;E组Ob-R表达较B、C、D组下降(P<0.05),与A组相比(P>0.05);E组β2-AR表达较B、C、D组升高(P<0.05),与A组相比(P>0.05)。结论 LP呈浓度依赖抑制大鼠气道平滑肌细胞β2-AR的表达。     

Age-dependent structural changes in human neuronal chromatin.

After partial digestion with micrococcal nuclease, DNA was extracted from nuclei of cerebral cortex neurons from young (23--36 y.) and old (78--85 y.) humans. The DNA fragments were subjected to gel electrophoresis, and their base-pair content determined. The nucleosomal DNA repeat length was found to increase from 170 (+/- 18) base-pairs in the young group to 199 (+/- 8) base-pairs in the old group. This increase of 29 base-pairs appears to be confined to the linker region of the nucleosomal DNA, since the core-DNA was always found to contain approx. 140 base-pairs. In addition, the amount of nuclear DNA digested by the micrococcal nuclease was observed to vary with age: after 30 min. of incubation at 37 degrees C hydrolysis of up to 80% of the nuclear DNA in the young but only up to 60% in the old neuronal nuclei was achieved. The age-dependent increase in chromosomal DNA repeat length is a direct proof of alterations in the basic chromatin structure with aging. It cannot be decided, however, whether the change in DNA digestibility is dependent on alterations of the chromatin basic structure, its superstructure, or both.     

Age-dependent changes in the mechanisms regulating dopamine uptake in the central nervous system

Na+-dependent binding of 3H-Cocaine is located on dopaminergic terminals and is related to the dopamine uptake system. Studies on senescent rats indicate a decrease in 3H-Cocaine binding density in the striatum. In the same tissue an increase in the Km for dopamine uptake is observed. These changes might be relevant in the age-dependent alterations in dopaminergic function.     

Age-dependent changes in the shear wave propagation through human skin

We studied the potential use of the in vivo frequency response of human volar forearm skin as a means for evaluating skin age. The velocity and damping length of waves on the skin surface were correlated with chronological age. One hundred and fifty subjects from 1 to 95 years of age were studied. For the frequency spectrum from 800 to 2000 Hz, there was a linear correlation between the velocity of propagation and age. At 2000 Hz, the y intercept was 11.4 m/second and the slope was 0.245 m/second/year, r = 0.5500, p less than 1 x 10(-7). There was no correlation of velocity with sex, skin color, obesity, sun exposure, physical activity, or inpatient status.     

Age-dependent changes of collagen and elastin content in human aorta and pulmonary artery

Collagen and elastin in the arterial wall are thought to show some age-dependent changes, and to relate with development of the arteriosclerotic lesion. Both aortas and the pulmonary trunks were collected from 137 autopsy cases. Biochemical determination of collagen and elastin content was carried out. Collagen and elastin of the aorta and the pulmonary artery showed no significant age-dependent changes. Elastin content of the pulmonary artery increases with age in the adult. This paper seems to be the first report of simultaneous estimation of collagen and elastin content of both the aorta and the pulmonary artery.     

Age-dependent enzymatic changes in human cerebral cortex (author's transl)]

Little information about the possible neurochemical-enzymatic changes occuring during aging of human brain is available. We, therefore, investigated the activity of various enzymes of human brains obtained at autopsy and covering a range from 19 to 91 years. Protein kinase, which mediates the information carried by the second messenger cAMP, does not show age-related changes of basal activity. Cyclic AMP-dependent activation of protein kinase remains nearly constant up to 60 years of life, but undergoes a distinct and progressive decline between 60 and 90 years. In corpus striatum no age-related changes of cyclic AMP-dependent protein kinase activity were observed. The activity of carbonic anhydrase demonstrates in both human cortex and corpus striatum an age-dependent decrease which also begins after the 6th decade of life. These neurochemical changes are similar to morphological and physiological changes occuring in the aging brain. They begin after the 60th year of life.     

Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function

OBJECTIVE: To evaluate the effects of aging on left ventricular (LV) geometry, collagen levels, matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) abundance, and myocardial fibroblast function. METHODS: Young (3-month-old; n=28), middle-aged (MA; 15-month-old; n=17), and old (23-month-old; n=16) CB6F1 mice of both sexes were used in this study. Echocardiographic parameters were measured; collagen, MMP, and TIMP levels were determined for both the soluble and insoluble protein fractions; and fibroblast function was evaluated. RESULTS: LV end-diastolic dimensions and wall thickness increased in both MA and old mice, accompanied by increased soluble protein and decreased insoluble collagen. Immunoblotting revealed differential MMP/TIMP profiles. Compared to MA levels, MMP-3, MMP-8, MMP-9, MMP-12, and MMP-14 increased, and TIMP-3 and TIMP-4 decreased in the insoluble fraction of old mice, suggesting increased extracellular matrix (ECM) degradative capacity. Fibroblast proliferation was blunted with age. CONCLUSION: This study, for the first time, identified specific differences in cellular and extracellular processes that likely contribute to age-dependent ECM remodeling.     

Age-dependent changes of stress-related immunosuppression

The present investigations on the influence of physical stress and physical training and on the influence of aging on 19-S-antibody producing spleen cells showed: 1. Physical stress causes a failing of immunity in mice, which had no training. The immune response can be diminished by physical stress before and after sensitization. The immunosuppressive effect of stress is greater, if it was placed after sensitization. There is a strict correlation between the immunosuppressive effect of physical stress and the time of maximum production of 19-S-antibodies. 2. The immunosuppressive effect of physical stress increases with increasing age. The protecting effect of physical training is lower in adult and old animals than in young mice. 3. There is an increase of antibody loaded spleen cells until an age of eight months. In elder mice the number of immunocytes decreases significantly. 4. The mortality rate is greater in stressed and trained young mice than in the adult and old animals. Supposing a better adaptation in young mice it is to be considered that the biologically better developed animals survived by selections.     

Age-dependent changes in the mechanisms controlling prolactin secretion and phosphatidylinositol turnover in male rats: effect of phosphatidylserine

The present study was undertaken in order to better characterize the functional state of anterior pituitary gland in young and old rats by using prolactin secretion and incorporation of radioactive phosphate into phosphatidylinositol (PI) as markers. The in vitro incorporation of radiolabeled phosphate into anterior pituitary PI was significantly (p less than 0.01) greater in young (3-5 months) than in aged (24-25 months) male Sprague-Dawley rats. No significant difference was found in the incorporation by pituitary tissue of 32P into phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Also, the extent of prolactin secretion from isolated pituitary was significantly greater in young than in aged rats, while the prolactin pituitary content was significantly higher in aged animals. In vitro dopamine (DA) decreased the incorporation of 32P into PI, both in young and old pituitary glands, and inhibited prolactin secretion into the incubation medium. Brain cortex-phosphatidylserine (BC-PS), a pharmacologically active purified phospholipid, capable of stimulating the dopaminergic system in the hypothalamus and of decreasing prolactin secretion both in humans and rats in vitro and in vivo, inhibited the incorporation of labeled phosphate into PI of pituitary glands from either young or old rats, but did not alter the prolactin secretion from the glands incubated in vitro. Baseline prolactin plasma levels did not differ significantly between young and old rats either when blood was collected from the trunk after decapitation or underwent sampling from chronically cannulated rats.(ABSTRACT TRUNCATED AT 250 WORDS)