Retinal ischemia-reperfusion(I/R)injury is associated with many ocular *** cell death,macrophage infiltration,and oxidative injury are complications in retinal I/R ***(SF),an isothiocyanate found in cruciferous vegeta...
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Retinal ischemia-reperfusion(I/R)injury is associated with many ocular *** cell death,macrophage infiltration,and oxidative injury are complications in retinal I/R ***(SF),an isothiocyanate found in cruciferous vegetables such as broccoli,has cytoprotective effects against oxidative stress and its effect is mediated by nuclear factor E2-related factor 2(Nrf2),a transcription factor,and heme oxygenase-1(HO-1),which is one of Nrf2 downstream target *** study was undertaken to investigate the neuroprotective mechanisms of SF in the retina I/R rat ***(12.5mg/kg)or vehicle(corn oil)was intraperitoneally administered once a day for 1 ***,retinal I/R was induced by increasing the intraocular pressure(IOP)to 130 mm Hg for 60 *** specific experiments,protoporphyrin IX zinc(Ⅱ)(Zn PP,30 mg/kg),an HO-1 inhibitor,was intraperitoneally administered at 24 h prior to *** protective effects of SF were evaluated by determining the morphology of the retina,counting the infiltrating inflammatory cells and the surviving retinal ganglion cells(RGCs)and amacrine cells,and measuring apoptosis in the retinal *** expression of Nrf2and HO-1 was examined by immunofluorescence analysis and Western blotting.I/R induced a marked increase of ROS generation,caused pronounced inflammation,increased the apoptosis of RGCs and amacrine cells and caused the thinning of the inner retinal layer(IRL),and these effects were diminished or abolished by SF ***,SF treatment significantly increased the nuclear accumulation of Nrf2 and the level of HO-1 expression in the retinas after I/R injury;however,.Zn PP diminished the protective effects of SF on I/R *** results suggested that SF had protective effects on I/R retinas,which were mediated,at least in part,by the activation of the Nrf2/HO-1 antioxidant pathway.
目的:检测载脂蛋白E基因敲除小鼠(apoE(-/-))血管外膜成纤维细胞中G蛋白信号调节因子(regulator of G protein signaling,RGS)3,5的变化,探讨其在动脉粥样硬化发病中的作用。方法:体外培养高脂喂养2周的apoE(-/-)小鼠和C57BL/6小鼠动脉...
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目的:检测载脂蛋白E基因敲除小鼠(apoE(-/-))血管外膜成纤维细胞中G蛋白信号调节因子(regulator of G protein signaling,RGS)3,5的变化,探讨其在动脉粥样硬化发病中的作用。方法:体外培养高脂喂养2周的apoE(-/-)小鼠和C57BL/6小鼠动脉外膜成纤维细胞,利用基因芯片技术分析RGS3,RGS5mRNA的变化,通过RT-PCR进一步验证。结果:基因芯片数据分析显示,apoE(-/-)小鼠成纤维细胞中RGS3表达下调,与C57BL/6小鼠比值为0.46。RGS5表达上调,与C57BL/6小鼠比值为2.25。RT-PCR结果显示apoE(-/-)小鼠成纤维细胞RGS3mRNA水平低于对照组小鼠(比值为0.78),RGS5mRNA水平高于对照组小鼠(比值为2.34),与基因芯片检测结果相比,变化方向一致。结论:apoE(-/-)小鼠血管外膜成纤维细胞中选择性RGS3降低和RGS5升高可能与外膜成纤维细胞的激活密切相关,从而参与了动脉粥样硬化的发生与发展,RGS有可能成为动脉粥样硬化药物治疗及基因治疗的新靶点。
NMDARs and ASIC1a both exist in central synapses and mediate important physiological and pathological conditions,but the functional relationship between them is *** we report several novel findings that may shed light...
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NMDARs and ASIC1a both exist in central synapses and mediate important physiological and pathological conditions,but the functional relationship between them is *** we report several novel findings that may shed light on the functional relationship between these two important receptor ***,NMDAR activation by either NMDA or OGD led to increased[Ca2+]i and greater apoptotic and necrotic cell deaths in cultured hippocampal neurons;these cell deaths were prevented by application of NMDAR ***,ASIC1a activation with p H6.0 ECS induced similar increases in apoptotic and necrotic cell deaths;these cell deaths were prevented by ASIC1a antagonists,and also by NMDAR *** increased[Ca2+]i leads to increased cell deaths and since NMDAR exhibits much greater calcium permeability than ASIC1a,these data suggest that ASIC1a-induced neuronal death is mediated through activation of ***,treatment of hippocampal cultures with both NMDA and acidic ECS induced greater cell deaths than either NMDA or acidic ECS treatment *** results suggest that ASIC1a activation up-regulates NMDAR *** data supporting the functional relationship between ASIC1a and NMDAR are found in our electrophysiology experiments in hippocampal slices,where stimulation of ASIC1a induced a marked increase in NMDAR EPSC amplitude,and inhibition of ASIC1a resulted in a decrease in NMDAR EPSC *** summary,we present evidence that ASIC1a activity modulates NMDAR function and exacerbates NMDAR-mediated neuronal death in brain *** findings are invaluable to the search for novel therapeutic targets in the treatment of brain ischemia.
Hydroxysafflor yellow A(HSYA)was reported to be neuroprotective both in middle cerebral artery occlusion(MCAO)animal model and in cultured cortical ***,the underlying mechanism remains *** has been known that mass...
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Hydroxysafflor yellow A(HSYA)was reported to be neuroprotective both in middle cerebral artery occlusion(MCAO)animal model and in cultured cortical ***,the underlying mechanism remains *** has been known that mass glutamate release and over stimulation of N-methyl-d-aspartate(NMDA)type glutamate receptors are the main cause of neuronaldeath inbrain *** patch-clamp recordings of mouse hippocampal slices,primary hippocampal cultures,Ca2+imaging,and Western blot approaches,we found that HSYA effectively inhibited NMDA rreceptor-mediated excitatory postsynaptic currents(NMDAR EPSCs)which had a half maximum inhibition of0μ*** was also suppressed presynaptic glutamate transmitter ***,HSYA suppressed NMDAR-mediated oxygen-glucose-deprivation(OGD)evoked long-term potentiation(LTP)which resemble the reperfusion damage in brain *** cell viability assay,HSYA attenuated NMDA induced apoptotic and necrotic cell death *** attenuation effect was HSYA concentration ***2+imaging experiments also exihibited that NMDA-evoked inctracellular Ca2+concentration([Ca2+]i)increase was distinctly reduced or even abolished by containing different concentration of HSYA in extracellular *** western blot assay,we found that the intracellular apoptotic signaling molecule,cleaved-caspase3,expression was also suppressed by ***,HSYA protected CA1pyramidal cells of hippocampus against NMDA receptor-mediated membrane depolarization currents in OGD *** together,our data for the first time give the direct evidences that HSYA inhibits NMDAR-mediated synaptic transmission in hippocampal slices and intracellular Ca2+increase evoked by NMDA in hippocampal cultures,exerting the neuronal protection effect in the condition of high concentration of extracellular NMDA or glutamate,such as in brain *** data indicate that HSYA has a strong neuronal protection effect on NMDAR-mediated excitotoxic death and migh
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