Objective:Alzheimer’s disease( AD) is the most common neurodegenerative disorder which is characterized by amyloid-β( Aβ) aggradation in the brain and impairment of cognitive function. Thioredoxin-1( Trx-1) is a re...Objective:Alzheimer’s disease( AD) is the most common neurodegenerative disorder which is characterized by amyloid-β( Aβ) aggradation in the brain and impairment of cognitive function. Thioredoxin-1( Trx-1) is a redox regulating protein,and plays roles in resisting the oxidative stress and protecting neurons. Our previous study found that Trx-1 improved the cognitive function of Parkinson’s Disease( PD) mice. Geranylgeranylacetone( GGA) is an antiulcer drug and induces the expression of Trx-1 in vivo and in vitro. However,whether Trx-1 improves cognitive functions in mice of APP/PS1 or GGA protects SH-SY5 Y cells from cytotoxicity induced by Aβ is still unknown. The objective of present is to investigate the roles of Trx-1 and GGA in inhibiting neurotoxicity of Aβ. Methods:We used MTT assay to test the cell viability induced by Aβ(25-35) and western blot to detect the expression of Trx-1 in SH-SY5 Y cells. Trx-1 overexpression transgenic mice were hybridized with APP/PS1 transgenic mice to get control,Trx-1,Tx-1/APP/PS1 and APP/PS1 mice. Then we used Morris water maze,high plus maze and object recognition test to detect the cognitive function of different kinds of mice. We also used RT-PCR and western blot to test the mRNA level and expression of Trx-1,APP,PS1 and Aβ. Results:In our present study,we demonstrated that Aβ(25-35) decreased the cell viability and the expression of Trx-1 in SH-SY5 Y cells. The cell viability and the expression of Trx-1 were reversed by GGA. Our results showed that the escape latency in APP/PS1 mice was longer when compared with the Trx-1/APP/PS1 mice in Morris water maze and high plus maze. Whereas navigational experiments in Morris water maze result showed that the total number of crossings and the percentage of time spent in the target quadrant were significantly decreased in APP/PS1 mice when compared to Trx-1/APP/PS1 mice. Object recognition test the discrimination index was significantly decreased in APP/PS1 mice when compared with Trx-1/APP/PS1 mice. The mRNA levels and the expression of APP,PS1 and Aβ were decreased in Trx-1/APP/PS1 mice when compared to APP/PS1 mice. Conclusion:These results suggest that GGA protects SH-SY5 Y cells from cytotoxicity induced by Aβ(25-35) and restored the expression of Trx-1. Trx-1 overexpression improves cognitive function of APP/PS1 mice. Trx-1 may be a potential therapeutic target for the clinical management of AD.展开更多
目的探究血清网膜素-1(Omentin-1,OMTN)、硫氧还蛋白1(Thioredoxin-1,Trx1)、小窝蛋白-1(caveolin-1,Cav-1)在高血压脑出血(hypertensive intra cerebral hemorrhage,HICH)患者中的表达及其对预后的预测价值。方法回顾性分析行微创血肿...目的探究血清网膜素-1(Omentin-1,OMTN)、硫氧还蛋白1(Thioredoxin-1,Trx1)、小窝蛋白-1(caveolin-1,Cav-1)在高血压脑出血(hypertensive intra cerebral hemorrhage,HICH)患者中的表达及其对预后的预测价值。方法回顾性分析行微创血肿清除术82例HICH患者作为研究对象,根据治疗后30 d恢复情况分为预后良好组(n=48例)、预后不良组(n=34例),比较2组入院时血清OMTN、Trx1、Cav-1水平及格拉斯哥昏迷量表(Glasgow coma scale,GCS)评分、Graeb脑室出血评分,并分析其相关性。采用受试者工作曲线分析预测价值,分析入院时各指标不同水平患者不良结局的危险度。结果预后良好组OMTN水平高于预后不良组,血清Trx1、Cav-1水平低于预后不良组(P<0.05);预后不良组入院时GCS评分低于预后良好组,Graeb评分高于预后良好组(P<0.05);血清Trx1、Cav-1水平与GCS评分呈负相关,与Graeb评分呈正相关,OMTN水平与GCS评分呈正相关,与Graeb评分负相关;各指标单独预测预后不良的AUC均>0.6,但各指标联合诊断的AUC最大,为0.857(P<0.05);入院时OMTN、Trx1、Cav-1高水平HICH患者预后不良的危险度是低水平的0.242、2.462、3.440倍。结论HICH患者入院时OMTN水平降低,血清Trx1、Cav-1水平升高,各指标联合检测对预后不良预测价值较高,可作为临床评估HICH患者预后情况的辅助指标。展开更多
文摘Objective:Alzheimer’s disease( AD) is the most common neurodegenerative disorder which is characterized by amyloid-β( Aβ) aggradation in the brain and impairment of cognitive function. Thioredoxin-1( Trx-1) is a redox regulating protein,and plays roles in resisting the oxidative stress and protecting neurons. Our previous study found that Trx-1 improved the cognitive function of Parkinson’s Disease( PD) mice. Geranylgeranylacetone( GGA) is an antiulcer drug and induces the expression of Trx-1 in vivo and in vitro. However,whether Trx-1 improves cognitive functions in mice of APP/PS1 or GGA protects SH-SY5 Y cells from cytotoxicity induced by Aβ is still unknown. The objective of present is to investigate the roles of Trx-1 and GGA in inhibiting neurotoxicity of Aβ. Methods:We used MTT assay to test the cell viability induced by Aβ(25-35) and western blot to detect the expression of Trx-1 in SH-SY5 Y cells. Trx-1 overexpression transgenic mice were hybridized with APP/PS1 transgenic mice to get control,Trx-1,Tx-1/APP/PS1 and APP/PS1 mice. Then we used Morris water maze,high plus maze and object recognition test to detect the cognitive function of different kinds of mice. We also used RT-PCR and western blot to test the mRNA level and expression of Trx-1,APP,PS1 and Aβ. Results:In our present study,we demonstrated that Aβ(25-35) decreased the cell viability and the expression of Trx-1 in SH-SY5 Y cells. The cell viability and the expression of Trx-1 were reversed by GGA. Our results showed that the escape latency in APP/PS1 mice was longer when compared with the Trx-1/APP/PS1 mice in Morris water maze and high plus maze. Whereas navigational experiments in Morris water maze result showed that the total number of crossings and the percentage of time spent in the target quadrant were significantly decreased in APP/PS1 mice when compared to Trx-1/APP/PS1 mice. Object recognition test the discrimination index was significantly decreased in APP/PS1 mice when compared with Trx-1/APP/PS1 mice. The mRNA levels and the expression of APP,PS1 and Aβ were decreased in Trx-1/APP/PS1 mice when compared to APP/PS1 mice. Conclusion:These results suggest that GGA protects SH-SY5 Y cells from cytotoxicity induced by Aβ(25-35) and restored the expression of Trx-1. Trx-1 overexpression improves cognitive function of APP/PS1 mice. Trx-1 may be a potential therapeutic target for the clinical management of AD.
文摘目的探究血清网膜素-1(Omentin-1,OMTN)、硫氧还蛋白1(Thioredoxin-1,Trx1)、小窝蛋白-1(caveolin-1,Cav-1)在高血压脑出血(hypertensive intra cerebral hemorrhage,HICH)患者中的表达及其对预后的预测价值。方法回顾性分析行微创血肿清除术82例HICH患者作为研究对象,根据治疗后30 d恢复情况分为预后良好组(n=48例)、预后不良组(n=34例),比较2组入院时血清OMTN、Trx1、Cav-1水平及格拉斯哥昏迷量表(Glasgow coma scale,GCS)评分、Graeb脑室出血评分,并分析其相关性。采用受试者工作曲线分析预测价值,分析入院时各指标不同水平患者不良结局的危险度。结果预后良好组OMTN水平高于预后不良组,血清Trx1、Cav-1水平低于预后不良组(P<0.05);预后不良组入院时GCS评分低于预后良好组,Graeb评分高于预后良好组(P<0.05);血清Trx1、Cav-1水平与GCS评分呈负相关,与Graeb评分呈正相关,OMTN水平与GCS评分呈正相关,与Graeb评分负相关;各指标单独预测预后不良的AUC均>0.6,但各指标联合诊断的AUC最大,为0.857(P<0.05);入院时OMTN、Trx1、Cav-1高水平HICH患者预后不良的危险度是低水平的0.242、2.462、3.440倍。结论HICH患者入院时OMTN水平降低,血清Trx1、Cav-1水平升高,各指标联合检测对预后不良预测价值较高,可作为临床评估HICH患者预后情况的辅助指标。
