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PPAR α/γ双重激动剂研究进展 总被引:1,自引:0,他引:1
目前临床上使用的贝特类降脂药物和噻唑烷二酮类胰岛素增敏剂分别是PPARα和γ激动剂,而PPARα/γ双重激动剂兼有贝特类及噻唑烷二酮类药物的特点,可以改善胰岛素抵抗、调节体内糖代谢、脂代谢,调控脂肪细胞的分化,有望成为治疗2型糖尿病的新型药物。本文介绍了近年来PPARα/γ双重激动剂的研究进展情况。 相似文献
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过氧化物酶体增殖物活化受体δ(PPARδ)是一个由配体激活的核转录因子,属于核激素受体(nuclear hormone receptor)超家族。PPARδ被激活后,能增加逆向胆固醇转运,调节脂质和糖类代谢。因此,PPARδ激动剂有可能成为肥胖、糖尿病、代谢综合征以及动脉粥样硬化等心血管疾病的有效治疗药物。本文对现有的天然及合成PPARδ激动剂进行综述。 相似文献
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目的探讨胶体金法检测EV71型病毒IgM抗体和检测EV71型病毒核酸的临床应用。方法胶体金法和PCR-荧光探针法联合检测EV71型病毒并对结果进行比较。结果胶体金法检测EV71型病毒IgM抗体和PCR-荧光探针法检测EV71型病毒核酸相比无显著差异(P>0.05)。结论胶体金法和PCR-荧光探针法联合检测EV71型病毒既能保证快速检测,又能提高准确性。 相似文献
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单利珍 《国外医学(药学分册)》2005,32(5):318-321
噻唑烷二酮(TZD)包括一系列具有2,4-噻唑烷二酮结构的化合物.它们均具有不同的侧链取代基,因而药理特点各有不同.最近发现一种化合物TZD18,一种兼具有改善胰岛素抵抗和降低甘油三酯、胆固醇作用的PPARα/γ的双重激动剂.本文综述了TZD18在脂质代谢方面的研究进展. 相似文献
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简要介绍糖尿病的现状和胰岛素增敏剂的种类和发展状况,PPARα和PPARγ的作用及与PPARα/γ双重激动剂的关系,新型抗糖尿病药物烷氧基苯丙酸类PPARα/γ双重激动剂和苯氧基异丁酸类PPARα/γ双重激动剂的最新进展,并对新型糖尿病药物PPARα/γ双重激动剂的未来提出展望。 相似文献
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目的:研究新型PPARα/γ双重激动剂C618H的抗2型糖尿病作用。方法:采用双荧光素酶报告基因系统,确证C618H对PPARα和PPARγ的激动活性;通过前脂肪细胞分化实验和降脂实验,进一步明确C618H的PPARα/γ双重激动作用;灌胃给药,观察C618H对db/db2型糖尿病小鼠的降糖降脂作用;PT—PCR方法研究C618H的作用机制。结果:C618H有较强的PPARα/γ双重激动活性;能够促进前脂肪细胞分化,降低高脂小鼠的血脂水平;对2型糖尿病小鼠有明显的降糖降脂作用;能够增加不同组织中脂蛋白脂酶(LPL)、脂肪组织特异的脂肪酸转运蛋白(aP2)和葡萄糖转运体4(GluT4)mRNA的表达。结论:C618H是PPARα/γ双重激动剂,对2型糖尿病具有较好的降糖降脂作用。 相似文献
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过氧化物酶增殖体活化受体(PPAR)是治疗2型糖尿病等人类代谢疾病的新靶点。与单一的PPARγ激动剂相比,PPARα/γ双重激动剂可以产生协同作用,更具有开发潜力。现综述α烷氧基苯基丙酸类、苯氧异丁酸类、苄基丙二酸衍生物类及其他类型的PPARα/γ双重激动剂的研究进展,并提出一些研究思路。 相似文献
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甘氨酸类化合物对PPARα及γ亚型的激活作用 总被引:1,自引:0,他引:1
目的利用适于PPAR转录激活效应检测的细胞模型,分析系列化合物对PPARα及γ亚型的活化作用。方法将PPARα(或PPARγ)表达质粒、报告基因质粒和内参照质粒共转染HepG2细胞,并以仅转染报告基因质粒和内参照质粒的细胞作为对照。5个化合物(LTD-1,3,4,6,7)分别以不同浓度作用于转染细胞24h,然后裂解细胞,测定细胞内报告基因质粒的荧光素酶活性,后者表示化合物对PPARα(或PPARγ)的激活强度。结果细胞模型稳定可靠,能够灵敏反映PPAR的特异激活效应。甘氨酸类化合物的检测表明,LTD-4、LTD-6、LTD-7均具有激活PPARα和PPARγ的双重效应,LTD-1则仅能激活PPARγ,而LTD-3对PPARα和PPARγ均无明显的激活作用。结论所建细胞模型适于PPARα和PPARγ转录激活作用的分析,化合物LTD-4,6,7具有激活PPARα和PPARγ的双重作用,为作为双激动剂先导化合物的深入研发提供了依据。 相似文献
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抗动脉粥样硬化药物研究进展 总被引:1,自引:0,他引:1
动脉粥样硬化是许多心血管疾病的主要病理基础之一。根据作用机制的不同,分类概述用于动脉粥样硬化治疗的ACAT抑制剂、胆汁酸吸收抑制剂、胆固醇合成抑制剂、抗氧化剂、PPAR激动剂、糜酶抑制剂等药物的研究近况。 相似文献
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Recent experimental evidence demonstrated an aberrant overexpression of cyclooxygenase-1 (COX-1) in various cancers, which has stimulated the development of COX-1-selective inhibitors as promising anticancer drugs and cancer imaging agents. Herein we describe the synthesis and validation of 3-(furan-2-yl)-N-aryl 5-amino-pyrazoles as a novel class of COX-1 inhibitors, including molecular docking studies. Among all tested compounds, 4-(5-azido-3-(furan-2-yl)-1H-pyrazol-1-yl)benzoic 17 displayed a favorable COX-1 inhibition and selectivity profile (COX-1 IC50 = 0.1 μM, SI >1000 over COX-2). Compound 17 was selected as a lead structure for developing the novel COX-1-selective fluorescent probe 22. Fluorescent probe 22 was prepared via click chemistry by installing a nitro-benzoxadiazole motif as a fluorophore into the 3-(furan-2-yl)-N-aryl 5-amino-pyrazole scaffold. Fluorescence probe 22 was tested in ovarian cancer cell line OVCAR-3, confirming its usefulness for targeting and visualizing COX-1 in living cells with confocal microscopy. 相似文献
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Lefrançois M Lefebvre MR Saint-Onge G Boulais PE Lamothe S Leduc R Lavigne P Heveker N Escher E 《ACS medicinal chemistry letters》2011,2(8):597-602
The development of agonists for the chemokine receptor CXCR4 could provide promising therapeutic candidates. On the basis of previously forwarded two site model of chemokine-receptor interactions, we hypothesized that linking the agonistic N-terminus of SDF-1 to the T140 backbone would yield new high-affinity agonists of CXCR4. We developed chimeras with the agonistic SDF-1 N-terminus grafted to a T140 side chain and tested their binding affinity and chemotactic agonist activity. While chimeras with the peptide grafted onto position 12 of T140 remained high-affinity antagonists, those bearing the peptide on position 14 were in part agonists. One chimera was a full CXCR4 agonist with 25 nM affinity, and several chimeras showed low nanomolar affinities with partial agonist activity. Our results confirmed that we have developed high-affinity agonists of CXCR4. 相似文献
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Jin M Saekusa Y Dewa Y Nishimura J Matsumoto S Shibutani M Hasumi K Mitsumori K 《Archives of toxicology》2009,83(2):173-181
Six-week-old rasH2 mice were injected intraperitoneally with N-diethylnitrosamine (DEN) after partial hepatectomy and administrated 0 or 6,000 ppm troglitazone (TRG) for 10 weeks. Relative
liver weight of females increased significantly in the DEN + TRG group compared to the DEN-alone group. The numbers of γ-glutamyltranspeptidase-
and proliferating cell nuclear antigen (PCNA)-positive cells tended to increase in both the sexes in the DEN + TRG group;
however, these changes were not significantly different from those in the DEN-alone group. Levels of gene expressions for
vascular endothelial growth factor (VEGF) and VEGFB (related to angiogenesis), tropomyosin 1 (Tpm1) and transforming growth
factor-β (related to ras/MAPK cascade activation), and PCNA (related to cell proliferation) in females were significantly
higher in the DEN + TRG than in the untreated control group but not in the DEN-alone group. Only Tpm1 gene had significantly
higher expression in the DEN + TRG group than in the DEN-alone group. These results suggest that rasH2 mice are not susceptible
to TRG in a two-stage hepatocarcinogenesis model. 相似文献