Background:Spontaneous intracerebral hemorrhage(ICH)is a severe cerebrovascular disease with high mortality,frequently accompanied by cerebral edema and acute kidney injury(AKI).Current treatment options remain limite...Background:Spontaneous intracerebral hemorrhage(ICH)is a severe cerebrovascular disease with high mortality,frequently accompanied by cerebral edema and acute kidney injury(AKI).Current treatment options remain limited.Methods:Active components and potential targets of Zhenwu Decoction(ZWD)were identified using multi-database screening.Protein-protein interaction(PPI)networks were constructed,and differentially expressed genes(DEGs)were analyzed using GEO datasets.Molecular docking and bioinformatics tools identified interactions between ZWD components and key targets,particularly AQP4 and AVPR1.Animal and cellular experiments validated the effects of ZWD on inflammation,oxidative stress,and apoptosis.Results:ZWD demonstrated significant modulation of AQP4 and AVPR1 expression,improving cerebral edema and renal function.Molecular docking confirmed ZWD’s active compounds interact strongly with these targets.In vivo studies revealed ZWD reduced oxidative stress and inflammatory responses,while in vitro experiments confirmed AVPR1’s role in apoptosis and inflammation,with ZWD significantly mitigating these adverse effects.Conclusion:This study is the first to demonstrate that ZWD alleviates cerebral edema following ICH by targeting AQP4 and AVPR1,offering new therapeutic insights for ICH management.展开更多
目的研究羟苯磺酸钙在高糖诱导的环境下对Müller细胞氧化损伤的保护作用及其机制。方法通过高糖诱导建立Müller细胞氧化损伤模型,并将细胞分为4组,即对照组(正常培养)、高糖组(35mmol/L葡萄糖培养基)、对照+羟苯磺酸钙组(常...目的研究羟苯磺酸钙在高糖诱导的环境下对Müller细胞氧化损伤的保护作用及其机制。方法通过高糖诱导建立Müller细胞氧化损伤模型,并将细胞分为4组,即对照组(正常培养)、高糖组(35mmol/L葡萄糖培养基)、对照+羟苯磺酸钙组(常规培养基础上加入0.5μmol/L羟苯磺酸钙)和高糖+羟苯磺酸钙组(高糖基础上加入0.5μmol/L羟苯磺酸钙)。使用CCK-8评估细胞增殖,流式细胞术检测细胞凋亡,试剂盒检测氧化应激指标,蛋白印迹技术检测内向整流钾离子通道4.1(inwardly rectifying K channel 4.1,Kir4.1)和水通道蛋白4(aquaporin-4,AQP4)蛋白水平。结果与对照组比较,高糖组Müller细胞增殖活性降低且凋亡率升高,细胞发生氧化应激,AQP4蛋白表达水平升高而Kir4.1蛋白表达水平降低(P<0.05)。与高糖组比较,高糖+羟苯磺酸钙组细胞增殖活性增加且凋亡率降低,细胞氧化应激损伤减轻,AQP4蛋白表达水平降低而Kir4.1蛋白表达水平升高(P<0.05)。结论羟苯磺酸钙可能通过调节AQP4/Kir4.1轴抑制高糖诱导的Müller细胞氧化损伤。展开更多
基金support from the Medical Discipline Construction Program of Shanghai Pudong New Area Health Commission(the Specialty Program)(Grant Number:PWZzb2022-21)The Academic Leaders Training Program of Shanghai Pudong New Area Health Commission(Grant Number:PWRd2022-14)+1 种基金The Scientific Research Program of Shanghai Pudong New Area Health Commission(the Achievement Transformation Program)(Grant Number:PW2023A-51)the Shanghai Pudong New Area Gongli Hospital Youth Fund Project(Grant Number:2020YQNJJ-16).
文摘Background:Spontaneous intracerebral hemorrhage(ICH)is a severe cerebrovascular disease with high mortality,frequently accompanied by cerebral edema and acute kidney injury(AKI).Current treatment options remain limited.Methods:Active components and potential targets of Zhenwu Decoction(ZWD)were identified using multi-database screening.Protein-protein interaction(PPI)networks were constructed,and differentially expressed genes(DEGs)were analyzed using GEO datasets.Molecular docking and bioinformatics tools identified interactions between ZWD components and key targets,particularly AQP4 and AVPR1.Animal and cellular experiments validated the effects of ZWD on inflammation,oxidative stress,and apoptosis.Results:ZWD demonstrated significant modulation of AQP4 and AVPR1 expression,improving cerebral edema and renal function.Molecular docking confirmed ZWD’s active compounds interact strongly with these targets.In vivo studies revealed ZWD reduced oxidative stress and inflammatory responses,while in vitro experiments confirmed AVPR1’s role in apoptosis and inflammation,with ZWD significantly mitigating these adverse effects.Conclusion:This study is the first to demonstrate that ZWD alleviates cerebral edema following ICH by targeting AQP4 and AVPR1,offering new therapeutic insights for ICH management.
文摘目的研究羟苯磺酸钙在高糖诱导的环境下对Müller细胞氧化损伤的保护作用及其机制。方法通过高糖诱导建立Müller细胞氧化损伤模型,并将细胞分为4组,即对照组(正常培养)、高糖组(35mmol/L葡萄糖培养基)、对照+羟苯磺酸钙组(常规培养基础上加入0.5μmol/L羟苯磺酸钙)和高糖+羟苯磺酸钙组(高糖基础上加入0.5μmol/L羟苯磺酸钙)。使用CCK-8评估细胞增殖,流式细胞术检测细胞凋亡,试剂盒检测氧化应激指标,蛋白印迹技术检测内向整流钾离子通道4.1(inwardly rectifying K channel 4.1,Kir4.1)和水通道蛋白4(aquaporin-4,AQP4)蛋白水平。结果与对照组比较,高糖组Müller细胞增殖活性降低且凋亡率升高,细胞发生氧化应激,AQP4蛋白表达水平升高而Kir4.1蛋白表达水平降低(P<0.05)。与高糖组比较,高糖+羟苯磺酸钙组细胞增殖活性增加且凋亡率降低,细胞氧化应激损伤减轻,AQP4蛋白表达水平降低而Kir4.1蛋白表达水平升高(P<0.05)。结论羟苯磺酸钙可能通过调节AQP4/Kir4.1轴抑制高糖诱导的Müller细胞氧化损伤。
