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国家自然科学基金(20572035)

作品数:6 被引量:21H指数:3
相关作者:罗贵民吕绍武牟颖闫岗林申斯乐更多>>
相关机构:吉林大学浙江大学长春西诺生物科技有限公司更多>>
发文基金:国家自然科学基金国家科技支撑计划中央级公益性科研院所基本科研业务费专项更多>>
相关领域:医药卫生理学自动化与计算机技术生物学更多>>

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Comparison Between the Effects of 2-Selenium Bridged β-Cyclodextrin and Ebselen on Treating SHRsp Stroke被引量:4
2008年
A glutathione peroxidase(GPX) mimic, 2-selenium bridged β-cyclodextrin(2-SeCD), was synthesized. In order to examine its role and mechanism in treating stroke we chose stroke-prone spontaneously hypertensive rats(SHRsp) as animal model. 56 SHRsps of 8-week olds were randomly divided into several groups: test groups (low, moderate, high dose of 2-SeCD) and control groups(positive and negative). After onset of the stroke, the rats in test groups were orally administrated with different amounts of 2-SeCD, the positive control group with ebselen, and the negative control group with drinking water. The treatment lasted two weeks, followed by observation of the rats for 10 days, meanwhile blood pressure, biochemical parameters of plasma, and the contents of nitric oxide(NO) and malondialdehyde(MDA) in plasma and brain were determined. The results show that there were significant differences in contents of NO and MDA in plasma and brain between the test groups(high, moderate dose of 2-SeCD) and negative control group. The NO contents of the test groups were obviously higher than that of the negative control group (P〈0.01). The MDA contents of the test groups(high, moderate dose of 2-SeCD) were obviously lower than that of the negative control group(P〈0.01). The mechanism of 2-SeCD in treating stroke was discussed, which maybe related to the increase of NO and the decrease of MDA in plasma and brain tissue, but the exact mechanism should be further studied. Moreover, the tendencies of changes in systolic blood pressure, contents of NO and MDA, and other physiological parameters for the test groups were shown to be much better than the corresponding parameters for the positive group(the group with ebselen)(P〈0.05), indicating that the treatment effect of 2-SeCD is better than that of ebselen.
JIA Zhi-dan LIN Feng LIU Lei MU Ying YAN Gang-lin LUO Gui-min
关键词:STROKE
Rapid Selection of Phage Se-scFv with GPX Activity via Combination of Phage Display Antibody Library with Chemical Modification
2007年
Glutathione peroxidase(GPX) plays an important role in scavenging reactive oxygen species. A series of catalytic antibodies with GPX activity have been generated by the authors of' this study. To obtain humanized catalytic antibodies, the phage-displayed human antibody library was used to select novel antibodies by repetitive screening, Phage antibodies, scFv-B8 and scFv-H6 with the GSH-binding site, were obtained from the library by enzyme-linked immu- nosorbent assay(ELISA) analysis with 4 rounds of scelection against their respective haptens, S-2,4-dinitriphenyl t-butyl ester(GStI-s-DNP-Bu) and S-2,4-dinit,-iphenyl t-hexyl ester(GSH-s-I)NP-He). Nevertheless, several studies need to be condueted to determine whether scFv-B8 and seFv-tI6 possess GPX activity. 1'o enhance the speed of the selection, selenocysteine(Sec, the catalytic group of GPX) was incorporated directly into the phages, scFv-B8 and seFv-H6, by chemical mutation to form the phages Se-scFv-B8 and Se-scFv-H6. The GPX activities were found to be 3012 units/μmol and 2102 units/μmol, respectively. To improve the GPX activity of the phage Se-scFv-B8, DNA shuffling was used to construct a secondary library and another positive phage antibody scFv-B9 was screened out by another panning against GSH-s-DNP-Bu. When Sec was incorporated via chemical mutation into the phage antibody scFv-B9, its GPX activity reached 3560 units/μmol, which is 1.17-fold higher than the phage antibody Se-scFv-B8 and almost approached the order of magnitude of native GPX. The rapid selection is the prerequisite for generating humanized Se-seFv with GPX activity.
LIN FengLI YingYANG Wen-kuiLIANG BingMU YingSUN YeLI WeiLUO Gui-min
关键词:SELECTION
含硒桥联环糊精诱导体外培养H22小鼠肝癌细胞凋亡的作用被引量:1
2009年
目的:研究含硒桥联环糊精(2-SeCD)对体外培养H22小鼠肝癌细胞凋亡的促进作用,探讨2-SeCD的抗肿瘤活性。方法:体外培养的H22细胞分别加入80、160、320和640μmol.L-12-SeCD作为实验组,并设阴性对照组。倒置相差显微镜观察细胞形态的变化;MTT法检测细胞生长抑制率,计算中效抑制浓度(IC50);流式细胞术(FCM)检测细胞周期和凋亡。结果:320和640μmol.L-12-SeCD组细胞生长抑制率分别为(25.90±2.13)%和(49.40±3.66)%,与对照组比较差异有显著性(P<0.01),2-SeCD 48 h的IC50为611.29μmol.L-1;320和640μmol.L-12-SeCD组凋亡率分别为5.52%和12.47%,2-SeCD可使细胞阻滞于G0/G1期。结论:2-SeCD可抑制H22细胞增殖并促进其凋亡,2-SeCD对肝癌具有潜在的治疗价值。
许新王冰梅王微潘宇林婷婷闫岗林罗贵民
关键词:细胞凋亡
新型兼具GPX,SOD,CAT活性的水杨醛Schiff碱衍生物的合成被引量:8
2009年
以5-磺基水杨醛为母体,经氯甲基化和硒化反应引入催化基团—SeH,此化合物经空气氧化、Schiff碱反应以及锰螯合反应,最终得到一种新型的水杨醛Schiff碱类谷胱甘肽过氧化物酶(GPX)模拟物.测定了该模拟物的红外光谱、核磁共振谱、质谱和抗氧化能力.此模拟物同时兼具超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性,水溶性好,保护线粒体免遭氧化损伤能力强,具有作为药物前体的潜力.
李唤民高楠刘磊申斯乐罗贵民
关键词:谷胱甘肽过氧化物酶水杨醛SCHIFF碱过氧化氢酶
谷胱甘肽过氧化物酶模拟物6-CySeCD对过氧化氢诱导小鼠成纤维细胞损伤的保护作用被引量:3
2010年
考察不同剂量的H2O2作用于小鼠成纤维细胞(NIH3T3)后,细胞脂质过氧化、存活率、DNA片段化的变化情况,并研究谷胱甘肽过氧化物酶(GPX)的模拟物6A,6B-环己胺-6A′,6B′-硒桥联-β-CD(6-CySeCD)抗H2O2诱导小鼠成纤维细胞损伤的能力.结果表明:H2O2对NIH3T3细胞有严重损伤;6-CySeCD能有效保护细胞,防止紫外线引起的损伤.
徐亚维闫岗林龚平生牟颖罗贵民杨佳吕绍武
关键词:模拟物过氧化氢成纤维细胞
表面等离子体子共振传感器研究谷胱甘肽过氧化物酶模拟物与底物的结合作用被引量:6
2008年
采用表面等离子体子共振(SPR)传感装置,固定入射角,以波长为变量,以CCD为检测系统,用对金有较强吸附作用的谷胱甘肽(GSH)为基底膜,研究了GSH分别与谷胱甘肽硫转移酶(GST)与小分子GPX模拟酶2-位-碲桥联-β-环糊精(2-TeCD)的动力学过程,计算得GSH与GST的结合常数为2.82×106L/mol;GSH与2-TeCD的结合常数为3.92×102L/mol。结果表明:本方法可以用来评价小分子GPX模拟酶与底物的结合程度,简便快捷,不需标记样品,可以实时监测反应过程,作用后酶与底物易于分离,分离后的酶可以继续使用等优点。
吕绍武金伟张莹高杨邹向宇李明牟颖阎岗林罗贵民金钦汉
关键词:传感器模拟酶底物
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