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国家重点基础研究发展计划(2011CB503903)

作品数:8 被引量:37H指数:3
相关作者:张幼怡李子健刘宁潘晨宇何鑫更多>>
相关机构:北京大学第三医院北京大学吉林大学第二医院更多>>
发文基金:国家重点基础研究发展计划国家自然科学基金北京市自然科学基金更多>>
相关领域:医药卫生生物学理学一般工业技术更多>>

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雌性小鼠骨髓移植给雄性小鼠后内源性骨髓细胞残存状态的研究
2014年
目的:以雌性小鼠骨髓移植给雄性小鼠的方法,通过检测雄性小鼠血细胞的Y染色体来明确内源性骨髓细胞的残存状态。方法:将雌性或雄性C57BL/6小鼠作为受体,实验组用[137Cs]照射,6 h后每只经尾静脉注射供体小鼠骨髓细胞1×107。统计骨髓移植后14 d动物的存活率,并通过眶静脉采血观察外周血白细胞数量的变化,检测受体雄性小鼠体内Y染色体基因水平的变化以明确骨髓移植的效果。结果:分别用1 000、950和900rad的照射剂量对受体小鼠进行照射后将供体小鼠的骨髓移植到受体小鼠体内,1 000和950 rad剂量时雌性受体小鼠可迅速恢复造血功能,而雄性受体小鼠则仅有48%的存活率。900 rad照射剂量骨髓移植后,雄性受体小鼠迅速恢复了造血功能,13 d后外周血白细胞计数基本恢复正常。移植后的雄性受体小鼠在5周内已检测不到外周血细胞Y染色体基因,表明雄性受体小鼠的骨髓被完全破坏,雌性供体小鼠的骨髓可完全替代受体雄性小鼠的骨髓并且发挥造血功能。结论:在照射剂量900 rad照射后,雄性小鼠可以作为骨髓移植受体,为将来应用雄性小鼠作为骨髓移植受体动物开展有关心血管疾病的研究奠定了实验基础。
张玲王梦雨黄薇刘国庆
关键词:骨髓移植性别
14-3-3ε蛋白磷酸化修饰的生物质谱分析被引量:3
2013年
本研究在HEK293细胞中过表达带有6个组氨酸标签的14-3-3ε蛋白,经镍离子亲和树脂富集和凝胶电泳等生物化学方法分离并富集目标14-3-3ε蛋白。利用特异性胰蛋白酶对14-3-3ε蛋白进行胶内水解后,采用TiO2亲和层析法,对蛋白水解混合物中的磷酸化修饰肽段进行富集,并利用生物质谱技术分析鉴定了14-3-3ε蛋白中的磷酸化修饰位点。结果表明,利用生物质谱技术,结合人工解谱的方法,能够高效、准确地鉴定HEK293细胞中过表达的14-3-3ε蛋白中的磷酸化修饰肽段的结构信息,确定了14-3-3ε蛋白中的12个磷酸化修饰位点,其中多个位点的磷酸化修饰为首次发现。
李子健何鑫潘晨宇刘宁
关键词:质谱磷酸化修饰
持续和间断激动β-肾上腺素受体对心脏重塑的不同作用
2011年
心脏疾病常伴有交感神经系统过度激活及循环系统内儿茶酚胺水平增高,通过激动β-肾上腺素受体引起心脏重塑.β-AR激动剂异丙基肾上腺素常用来制备心脏重塑模型.然而β-AR不同的激动模式,脉冲式的间断激动与慢性持续激动对心脏重塑和心脏功能下降的影响是否不同,尚未见报道.为此,本研究比较了ISO间断给药与持续给药对小鼠心脏重塑和功能的影响.通过两种不同给药模式给予小鼠为期两周的ISO(5mgkg-1天-1)处理:每天皮下注射或通过微渗泵皮下持续输注.心脏重塑和功能通过超声心动图、血流动力学检测及组织学分析进行评价.相关信号分子通过蛋白免疫印迹和实时定量聚合酶链反应进行检测.结果表明,两种不同给药模式引起小鼠心肌肥厚的程度类似(心脏重量/体重比值:皮下注射组增加16%,埋泵组增加19%).但是,与埋泵组相比,ISO皮下注射组引起的心脏纤维化程度更重,并较早发生心脏功能下降.促纤维化因素,包括结缔组织生长因子和NADPH氧化酶亚单位NOX4的表达量在ISO皮下注射组都显著高于埋泵组.综上,与β-AR持续激动相比,β-AR间断激动引起心脏纤维化更重,并更易引起心脏功能失代偿.本研究结果为阐明β-AR不同激动模式在心脏病理重塑中的作用提供了新的视角,并为用肾上腺素受体激动剂复制心脏疾病模型的模式选择提供参考依据.
马晓伟宋峣陈超陈超付勇南沈蔷李子健
关键词:Β-肾上腺素受体NADPH心肌肥厚心肌纤维化
Applications of nanotechnology in biomedicine被引量:1
2013年
Nanomedicine is the application of nanotechnology in treatment,diagnosis,monitoring and control of biological systems,and is at the leading-edge of clinical medicine and preclinical research.Increasing attention has been paid to the application of nanotechnology in medicine recently(Figure 1).Nanotechnology means the control of matter and processes at a nanoscale(1–100 nm)in one or more dimen-
WU JiMinLI ZiJian
关键词:生物医学生物系统
Distinct actions of intermittent and sustained β-adrenoceptor stimulation on cardiac remodeling被引量:15
2011年
Heart disease is associated with increased sympathetic nerve activity and elevated levels of circulating catecholamines,resulting in chronic stimulation of the β-adrenergic receptors (β-AR) and consequent pathological cardiac remodeling.Experimentally,chronic administration of the β-AR agonist isoproterenol (ISO) has been most commonly used to model β-AR-induced cardiac remodeling.However,it remains unclear whether β-AR-mediated cardiac remodeling and dysfunction differs between sustained versus pulsatile (intermittent) exposure to a β-agonist.Here,we compare the effects of intermittent versus sustained administration of ISO on cardiac remodeling and function in mice.Animals were administered 5 mg (kg d)-1 ISO for 2 weeks either by daily subcutaneous injection,or continuous infusion via an implanted osmotic minipump.Cardiac function and remodeling were determined by echocardiography,micromanometry and histology.Moreover,Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were utilized to define the proteins and genes involved.Both sustained and intermittent administration of ISO resulted in a similar degree of cardiac hypertrophy (16% and 19%,respectively).However,mice receiving ISO by daily injection developed more severe ventricular systolic and diastolic dysfunction and myocardial fibrosis compared with mice receiving ISO via the osmotic minipump.The disparity in results between the delivery methods is suggested to be due,at least in part,to increased expression of fibrogenic factors,including connective tissue growth factor (CTGF) and NADPH oxidase (NOX4),in mice receiving intermittent application of ISO.In summary,compared with sustained exposure to a β-AR agonist,intermittent β-AR stimulation leads to more severe cardiac dysfunction and fibrosis.These findings not only further our understanding of β-AR function in the setting of cardiac pathophysiology,but also highlight that significant differences can result dependent upon the mode of experimental β-AR stimulation in
MA XiaoWei1,3,SONG Yao1,3,CHEN Chao1,3,FU YongNan1,3,SHEN Qiang2,3,LI ZiJian1,3 & ZHANG YouYi1,3 1Institute of Vascular Medicine,Peking University Third Hospital,Beijing 100191,China
关键词:肾上腺素受体心肌重塑NADPH氧化酶
HIP-55作为分子开关蛋白质调控细胞凋亡
HIP-55[hematopoietic progenitor kinase1(HPK1)-interacting protein of55 kDa]是一个包含多功能域的蛋白质。HIP-55是一个重要的信号转导分子,主要...
李子健张幼怡Haian Fu
关键词:细胞凋亡
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Glycine attenuates myocardial ischemia-reperfusion injury by inhibiting myocardial apoptosis in rats被引量:10
2012年
Glycine is a well-documented cytoprotective agent.However,whether it has a protective effect against myocar-dial ischemia-reperfusion injury in vivo is still unknown.By using an open-chest anesthetized rat model,we found that glycine reduced the infarct size by 21% in ischemia-reperfusion injury rats compared with that in the vehicle-treated MI/R rats.The left ventricular ejection fraction and fractional shortening were increased by 19.11% and 30.98%,respectively,in glycine-treated rats.The plasma creatine kinase levels in ischemia-reperfusion injury rats decreased following glycine treatment.Importantly,administration of glycine significantly inhibited apoptosis in post-ischemia-reperfusion myocardium,which was accompanied by suppression of phosphorylated p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase,as well as the Fas ligand.These results suggest that gly-cine attenuates myocardial ischemia-reperfusion injury in vivo by inhibiting cardiomyocytes apoptosis.
Xiaozheng ZhongXiaoyu LiLingling QianaYiming XuYan LuJing ZhangNan LiXudong ZhuJingjing BenQing YangQi Chen
关键词:GLYCINEAPOPTOSISCARDIOMYOCYTES
Genetic variants of the class A scavenger receptor gene are associated with coronary artery disease in Chinese
2012年
The class A scavenger receptor, encoded by the macrophage scavenger receptor 1 (MSR1) gene, is a pattern recognition receptor (PPR) primarily expressed in macrophages. It has been reported that genetic polymorphisms of MSR1 are significantly associated with the number of diseased vessels and coronary artery narrowing greater than 20% in Caucasians. However, whether it links genetically to coronary artery disease (CAD) in Chinese is not defined. Here, we performed an independent case-control study in a Chinese population consisting of 402 CAD cases and 400 controls by genotyping ten single nucleotide polymorphisms (SNPs) of MSR1. We found that rs416748 and rs13306541 were significantly associated with an increased risk of CAD with per allele odds ratio (OR) of 1.56 [95% confidence interval (CI) = 1.28-1.90; P 〈 0.001] and 1.70 (95% CI = 1.27-2.27; P 〈 0.001), re- spectively. Our results indicate that genetic variants of MSR1 may serve as predictive markers for the risk of CAD / in combination with traditional risk factors of CAD in Chinese population.
Min ZhangYan ZhangShuaishuai ZhuXiaoyu LiQing YangHui BaiQi Chen
二甲双胍的心脏保护作用机制研究进展被引量:8
2011年
二甲双胍是一个古老的药物。早在中世纪的欧洲,人们发现一种名叫法国丁香(French lilac,Galega officinalis)的植物可以缓解伴有尿多症状的疾病--即现在所称的糖尿病[1]。后来发现,这种植物中起到降糖作用的活性成分是胍类物质(guanidine)[2]。1922年爱尔兰的科学家将法国丁香中具有降血糖作用的成分二甲双胍首次合成成功,1957年二甲双胍在法国首次获准作为降糖药用于临床。现在二甲双胍类药物是2型糖尿病一线治疗药物,广泛应用于临床。二甲双胍的降糖作用主要是通过减少肝脏葡萄糖产生[大部分作用是通过抑制糖异生(gluconeogenesis),另有小部分作用是抑制糖原分解(glycogenolysis)]以及增强胰岛素刺激下的外周组织(骨骼肌和脂肪组织)对葡萄糖的摄取[3-5],减少小肠葡萄糖的吸收[6]。
张幼怡
关键词:二甲双胍TGFAMPK降糖作用心脏保护
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