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国家自然科学基金(81070212)

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Predictive role of cerebrospinal fluid hydrogen sulfide in central nervous system leukemia被引量:10
2011年
Background Central nervous system leukemia (CNSL) is an important relapse in children with acute lymphoblastic leukemia (ALL). We investigated the possible role of endogenous hydrogen sulfide (H2S) of cerebrospinal fluid (CSF) in predicting CNSL. Methods From August 2008 to December 2010, 380 children were enrolled in this study at Shijitan Hospital, China. These children were from 2 to 16 years old, and the median age was 6.5 years. They were divided into a CNSL group (7 cases), a leukemia group (307 cases), a non-leukemia group (26 cases) and a healthy group (40 children). CSF specimens were obtained from conventional lumbar punctured, then centrifuged and supernatants preserved for H2S detection. Leukemic cells precipitates from CSF were found in three cases, the hCSE and hCBS mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR), and H2S levels in serum were also measured. The receiver operating characteristic (ROC) curve and area under curve (AUC) were used to assess the predictive diagnosis role of CSF H2S in children with ALL and CNSL. Results The serum H2S contents of the CNSL and leukemia groups were (96.98±15.77) pmol/L and (93.35±17.16) μmol/L respectively, much higher than those of healthy, (44.29±2.15) pmol/L, and non-leukemia, (46.32±6.54) μmol/L, groups (P 〈0.01). Compared with the leukemia group, CSF H2S content of the CNSL group was significantly high (P 〈0.01). Meanwhile, in contrast to the non-leukemia group, CSF H2S contents of the CNSL and leukemia groups were both significantly increased (P 〈0.01). In addition, leukemic cells from CSF precipitations could express CBS and CSE mRNA. Furthermore, the ROC analysis showed the UAC was 0.929 (95% CI: 0.857-1.000), and the optimum cut-off value of CSF H2S was 12.08μmol/L, and the sensitivity and specificity were 83.3% and 97.2% respectively. Conclusions CSF H2S contents were significantly increased in children with CNSL. Afte
DU Shu-xuXIAO JiangGUAN FengSUN Li-mingWU Wan-shuiTANG HongDU Jun-baoTANG Chao-shuJIN Hong-fang
关键词:CHILDLEUKEMIA
H_2S对氧化型低密度脂蛋白诱导人单核巨噬细胞核转录因子-κB的影响及机制被引量:1
2013年
目的:研究硫化氢(hydrogen sulfide,H2S)对氧化型低密度脂蛋白(oxidized low-density lipoprotein,ox-LDL)诱导人单核巨噬细胞NF-κB通路的调节作用及其机制。方法:人单核细胞系THP-1细胞采用12-豆蔻酸-13-乙酸佛波醇(phorbol myristate acetate,PMA)诱导分化为巨噬细胞后,分为4组:对照组、ox-LDL组、ox-LDL+H2S100μmol/L组及ox-LDL+H2S 500μmol/L组。用Western blot检测细胞IκBα蛋白表达及NF-κB磷酸化水平,激光共聚焦法检测细胞胞浆IκBα及NF-κB的核转位改变,免疫共沉淀方法检测细胞核中NF-κB p65与IκBα结合情况。结果:Western blot结果显示,与对照组相比,ox-LDL组人单核巨噬细胞中NF-κB p65磷酸化水平明显升高(0.855±0.116 vs.0.502±0.218,P=0.046),IκBα表达明显减少(0.612±0.216 vs.0.997±0.167,P=0.029);与ox-LDL组相比,ox-LDL+H2S 100μmol/L组及ox-LDL+H2S 500μmol/L组细胞中NF-κB p65磷酸化水平显著降低(0.424±0.225 vs.0.855±0.116,P=0.020;0.378±0.071 vs.0.855±0.116,P=0.011),IκBα表达显著增多(1.037±0.111 vs.0.612±0.216,P=0.015;1.046±0.084 vs.0.612±0.216,P=0.013)。激光共聚焦结果显示:与对照组相比,ox-LDL组THP-1源性巨噬细胞胞浆中IκBα表达明显降低,NF-κB p65核转位明显增加;与ox-LDL组相比,ox-LDL+H2S 100μmol/L组及ox-LDL+H2S 500μmol/L组细胞胞浆IκBα表达显著增多,NF-κBp65核转位明显减少。免疫共沉淀结果显示,对照组人单核巨噬细胞胞核内未检测到NF-κB p65与IκBα的结合,ox-LDL组细胞核内NF-κB p65与IκBα结合较少,ox-LDL+H2S 100μmol/L组及ox-LDL+H2S 500μmol/L组细胞核内NF-κB与IκBα结合明显增多。结论:H2S可抑制ox-LDL诱导人单核巨噬细胞中NF-κB通路激活,其作用机制可能与抑制胞浆中IκBα降解,减少NF-κB p65磷酸化激活及核转位,同时可促进胞核中IκBα与NF-κB的结合,进而抑制NF-κB的活性有关。
赵曼曼张巧丽闫辉杜军保耿彬唐朝枢金红芳
关键词:氧化低密度脂蛋白单核细胞巨噬细胞
Hydrogen sulfide and vascular relaxation被引量:5
2011年
Objective To review the vasorelaxant effects of hydrogen sulfide (H2S) in arterial rings in the cardiovascular system under both physiological and pathophysiological conditions and the possible mechanisms involved. Data sources The data in this review were obtained from Medline and Pubmed sources from 1997 to 2011 using the search terms "hydrogen sulfide" and "vascular relaxation". Study selection Articles describing the role of hydrogen sulfide in the regulation of vascular activity and its vasorelaxant effects were selected. Results H2S plays an important role in the regulation of cardiovascular tone. The vasomodulatory effects of H2S depend on factors including concentration, species and tissue type. The H2S donor, sodium hydrosulfide (NariS), causes vasorelaxation of rat isolated aortic rings in a dose-dependent manner. This effect was more pronounced than that observed in pulmonary arterial rings. The expression of KATp channel proteins and mRNA in the aortic rings was increased compared with pulmonary artery rings. H2S is involved in the pathogenesis of a variety of cardiovascular diseases. Downregulation of the endogenous H2S pathway is an important factor in the pathogenesis of cardiovascular diseases. The vasorelaxant effects of H2S have been shown to be mediated by activation of KATP channels in vascular smooth muscle cells and via the induction of acidification due to activation of the Cr/HCO3 exchanger. It is speculated that the mechanisms underlying the vasoconstrictive function of H2S in the aortic rings involves decreased NO production and inhibition of cAMP accumulation. Conclusion H2S is an important endogenous gasotransmitter in the cardiovascular system and acts as a modulator of vascular tone in the homeostatic regulation of blood pressure.
SUN Yan TANG Chao-shu DU Jun-bao JIN Hong-fang
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