目的探究半乳糖凝集素-3 (Galectin-3)介导的脑源性神经营养因子(brain-derived neurtrophicfactor,BDNF)/酪氨酸激酶受体B(tyrosine kinase receptor B,TrkB)通路在大鼠精神分裂症发病机制中的作用。方法将24只大鼠随机分为模型(M)组(n...目的探究半乳糖凝集素-3 (Galectin-3)介导的脑源性神经营养因子(brain-derived neurtrophicfactor,BDNF)/酪氨酸激酶受体B(tyrosine kinase receptor B,TrkB)通路在大鼠精神分裂症发病机制中的作用。方法将24只大鼠随机分为模型(M)组(n=12)和对照(C)组(n=12),使用MK-801诱导M组建立大鼠精神分裂症模型,C组给予等量生理盐水。1周后,采用旷场和强迫游泳实验评估大鼠行为变化,Morris水迷宫实验检测认知功能,免疫组化测定脑组织Galectin-3和BDNF表达,western blotting和RT-PCR法检测海马Galectin-3、BDNF和TrkB蛋白含量及mRNA水平变化。结果 M组大鼠和C组比较,穿越格数减少(23.25±3.09 vs. 55.25±6.13,P<0.001),游泳不动时间延长[(122.50±6.95)s vs.(89.00±6.68)s,P<0.001]。水迷宫实验显示M组逃避潜伏期时间高于C组[(26.36±4.62)s vs.(14.64±3.72)s],穿越平台次数也低于C组(2.75±0.96 vs. 8.25±1.26),差异均有统计学意义(P<0.001)。M组大鼠海马区Galectin-3蛋白含量(0.83±0.04 vs. 0.34±0.05)及mRNA水平(3.79±0.82 vs. 1.02±0.12)较C组上调,BDNF与TrkB蛋白含量(0.40±0.05 vs. 0.77±0.04;0.24±0.06 vs. 0.52±0.06)及mRNA水平(0.46±0.09 vs. 1.01±0.07;0.37±0.04 vs. 1.02±0.24)降低,差异均有统计学意义(P<0.05)。结论精神分裂症大鼠海马组织中Galectin-3高表达,精神分裂症BDNF/TrkB功能异常、海马神经元损伤可能与其过度表达有关。展开更多
Glucagon-like peptide-1 receptor （GLP-1R） agonists are widely used for treating type 2 diabetes mellitus （T2DM） be- cause of their glucose-lowering and weight-losing effects, and low risk of hypoglycemia. Hence, t...Glucagon-like peptide-1 receptor （GLP-1R） agonists are widely used for treating type 2 diabetes mellitus （T2DM） be- cause of their glucose-lowering and weight-losing effects, and low risk of hypoglycemia. Hence, there is considerable interest in understanding the mechanism underlying the beneficial effects of GLP-I and developing stable and effective GLP-1R agonists. Here, we summarize the presently known mechanism of GLP-I actions, which are mainly through regulating cAMP-PKA signaling pathway; the latest developments in novel clinical GLP-1R agonists are also introduced, which are characterized with multiple properties, such as extended half-life, reduced side-effects, lower production costs and more convenient drug dosing mode. The potential risk of GLP-I-based therapeutics, an often-ignored fact, is also discussed.展开更多
文摘目的探究半乳糖凝集素-3 (Galectin-3)介导的脑源性神经营养因子(brain-derived neurtrophicfactor,BDNF)/酪氨酸激酶受体B(tyrosine kinase receptor B,TrkB)通路在大鼠精神分裂症发病机制中的作用。方法将24只大鼠随机分为模型(M)组(n=12)和对照(C)组(n=12),使用MK-801诱导M组建立大鼠精神分裂症模型,C组给予等量生理盐水。1周后,采用旷场和强迫游泳实验评估大鼠行为变化,Morris水迷宫实验检测认知功能,免疫组化测定脑组织Galectin-3和BDNF表达,western blotting和RT-PCR法检测海马Galectin-3、BDNF和TrkB蛋白含量及mRNA水平变化。结果 M组大鼠和C组比较,穿越格数减少(23.25±3.09 vs. 55.25±6.13,P<0.001),游泳不动时间延长[(122.50±6.95)s vs.(89.00±6.68)s,P<0.001]。水迷宫实验显示M组逃避潜伏期时间高于C组[(26.36±4.62)s vs.(14.64±3.72)s],穿越平台次数也低于C组(2.75±0.96 vs. 8.25±1.26),差异均有统计学意义(P<0.001)。M组大鼠海马区Galectin-3蛋白含量(0.83±0.04 vs. 0.34±0.05)及mRNA水平(3.79±0.82 vs. 1.02±0.12)较C组上调,BDNF与TrkB蛋白含量(0.40±0.05 vs. 0.77±0.04;0.24±0.06 vs. 0.52±0.06)及mRNA水平(0.46±0.09 vs. 1.01±0.07;0.37±0.04 vs. 1.02±0.24)降低,差异均有统计学意义(P<0.05)。结论精神分裂症大鼠海马组织中Galectin-3高表达,精神分裂症BDNF/TrkB功能异常、海马神经元损伤可能与其过度表达有关。
基金Supported by the Natural Science Foundation of China(81172971,81222043)the Program for New Century Excellent Talents in University(NECT11-0170)+2 种基金the Municiple Key Technology Program of Wuhan(Wuhan Bureau of Science & Technology,201260523174)the Clinical Research Foundation of the Health Bureau of Wuhan(WX12B06)the Natural Science Foundation of Hubei Province(2013CFB359)
文摘Glucagon-like peptide-1 receptor （GLP-1R） agonists are widely used for treating type 2 diabetes mellitus （T2DM） be- cause of their glucose-lowering and weight-losing effects, and low risk of hypoglycemia. Hence, there is considerable interest in understanding the mechanism underlying the beneficial effects of GLP-I and developing stable and effective GLP-1R agonists. Here, we summarize the presently known mechanism of GLP-I actions, which are mainly through regulating cAMP-PKA signaling pathway; the latest developments in novel clinical GLP-1R agonists are also introduced, which are characterized with multiple properties, such as extended half-life, reduced side-effects, lower production costs and more convenient drug dosing mode. The potential risk of GLP-I-based therapeutics, an often-ignored fact, is also discussed.
