目的分析急性脑梗死患者沉默信息调节因子2(silent information regulator 2,SIRT2)与认知功能障碍发生及病情程度的关系。方法回顾性选择2022年5月至2024年5月武汉市第一医院神经内科收治的急性脑梗死合并认知功能障碍患者150例(研究...目的分析急性脑梗死患者沉默信息调节因子2(silent information regulator 2,SIRT2)与认知功能障碍发生及病情程度的关系。方法回顾性选择2022年5月至2024年5月武汉市第一医院神经内科收治的急性脑梗死合并认知功能障碍患者150例(研究组),研究组依据认知功能障碍严重程度分为轻度组45例、中度组66例和重度组39例。另选取同期武汉市第一医院就诊的急性脑梗死未合并认知功能障碍患者125例(对照组)。采用Spearman相关性分析血清SIRT2水平与认知功能障碍及病情程度的相关性,ROC曲线分析血清SIRT2水平对认知功能障碍及病情的评估价值,并计算曲线下面积(area under curve,AUC)。结果研究组血清SIRT2水平明显高于对照组,差异有统计学意义[(20.38±5.19)mg/L vs(14.66±4.49)mg/L,P<0.05]。重度组血清SIRT2水平明显高于中度组和轻度组,中度组血清SIRT2水平明显高于轻度组,差异有统计学意义(P<0.05)。Spearman相关性分析显示,血清SIRT2水平与认知功能障碍发生及严重程度呈正相关(r=0.510,r=0.527,P<0.01)。ROC曲线分析显示,血清SIRT2水平评估急性脑梗死患者认知功能障碍发生的AUC为0.796(95%CI:0.743~0.842),临界值为19.0 mg/L,敏感性为63.33%,特异性为84.00%;血清SIRT2水平评估急性脑梗死患者认知功能障碍严重程度的AUC为0.747(95%CI:0.655~0.824),临界值为17.2 mg/L,敏感性为75.76%,特异性为71.11%(P<0.05)。结论急性脑梗死患者血清SIRT2水平与认知功能障碍发生及病情密切相关。展开更多
目的探讨沉默信息调节因子2相关酶2(silent information regulator 2 related enzyme 2,SIRT2)基因沉默对肝癌细胞增殖的影响及分子机制。方法利用慢病毒介导的shRNA干扰技术,靶向沉默SIRT2基因的表达;Western blot检测SIRT2基因沉默效...目的探讨沉默信息调节因子2相关酶2(silent information regulator 2 related enzyme 2,SIRT2)基因沉默对肝癌细胞增殖的影响及分子机制。方法利用慢病毒介导的shRNA干扰技术,靶向沉默SIRT2基因的表达;Western blot检测SIRT2基因沉默效果及SIRT2沉默后β-catenin蛋白的表达变化;流式细胞计数检测SIRT2基因沉默后肝癌细胞周期的变化,CCK-8法检测SIRT2基因沉默对肝癌细胞增殖的影响,台盼蓝计数检测SIRT2基因沉默及过表达β-catenin后,SIRT2基因沉默对肝癌细胞增殖的影响;BrdU实验检测SIRT2基因沉默对肝癌细胞DNA合成的影响;平板集落实验检测SIRT2沉默对肝癌细胞克隆形成能力的影响。结果 SIRT2 shRNA靶向沉默显著抑制肝癌细胞SIRT2的表达水平,shRNA沉默组肝癌细胞PLC-5的增殖能力较对照组分别下降48.3%(shSIRT2-1)、55.6%(shSIRT2-2)(P<0.01);SIRT2基因沉默后,肝癌细胞出现G1期阻滞,β-catenin蛋白表达水平下降;过表达β-catenin后SIRT2基因沉默组较对照组肝癌细胞增殖分别升高了89%(shSIRT2-1)、75%(shSIRT2-2)(P<0.01)。结论 SIRT2沉默可能通过调节β-catenin信号通路来影响肝癌细胞增殖。展开更多
OBJECTIVE To investigate icariside(ICS)Ⅱ protects against PC12 cel damage induced by oxygen-glucose deprivation and reoxygenation and explore its mechanism.METHODS The oxidative stress injury model was induced by oxy...OBJECTIVE To investigate icariside(ICS)Ⅱ protects against PC12 cel damage induced by oxygen-glucose deprivation and reoxygenation and explore its mechanism.METHODS The oxidative stress injury model was induced by oxygen-glucose deprivation/reoxygenation(OGD/R) 2 h/24 h in PC12 cells.N-acetyl-lcysteine(NAC),a classical anti-oxidant,was used as positive control.Pharmacodynamic experimental study groups as follows:control,control+ICS Ⅱ50 μmol·L^(-1),OGD/R,OGD/R+ICSⅡ 12.5 μmol·L^(-1),OGD/R + ICS Ⅱ 25 μmol·L^(-1),OGD/R + ICS Ⅱ50 μmol·L^(-1),and OGD/R+NAC 100 μmol·L^(-1) groups.Cell viability and lactate dehydrogenase(LDH) leakage rate were measured by MTT assay and LDH ELISA kit,respectively.Moreover,reactive oxygen species(ROS) ELISA kit was used for detection of intracellular ROS generation,Mito-SOX fluorescence staining was used for detecting production of ROS in mitochondria and mitochondrial membrane potential(MMP)was detected by rhodamine 123 dye.In addition,PC12 cells apoptosis was detected by one-step TUNEL assay.Furthermore,the expressions of nuclear factor erythroid 2-related factors(Nrf2),Keap1,HO^(-1),NQO^(-1),silent information regulator 3(SIRT3),IDH2,Bax,Bcl-2 and caspase 3 were detected by Western blotting analysis.RESULTS The results of MTT and LDH assay showed that OGD/R reduced the cell viability and improved LDH release compared with the control or ICSⅡ 50 μmol·L^(-1) alone(P<0.01).Meanwhile,OGD/R not only increased intracellular and mitochondrial ROS generation,but also elevated the fluorescence intensity of TUNEL staining,at the same time,the MMP was declined when challenged by OGD/R.Furthermore,the Western blotting results showed that OGD/R induced the increase in the expression of cytoplasm-Nrf2,Keap1,Bax and cleaved-caspase 3 level,while the decrease in the expression of nucleus-Nrf2,HO^(-1),NQO^(-1),SIRT3,IDH2 and Bcl-2(P<0.05).However,ICS Ⅱ significantly increased the viability of PC12 cells and reduced LDH leakage(P<0.01).Notably,ICS Ⅱ also suppressed ROS generation both in the intracellular and mitochondria,as well as restored MMP.It was also worthy to note that ICS Ⅱ decreased the expressions of cytoplasmNrf2,Keap1,Bax and the level of cleaved-caspase3,whereas,it increased the expressions of nucleus-Nrf2,HO^(-1),NQO^(-1),SIRT3,IDH2 and Bcl-2(P<0.05).CONCLUSION ICSⅡ reduced OGD/Rinduced oxidative damage in PC12 cells under the laboratory conditions,and its underlying mechanism may be related to the regulation of Nrf2/SIRT3 signaling pathway.展开更多
沉默信息调节因子2同源体1(silent mating type information regulation 2 homolog 1,SIRT1)基因作为一种编码组蛋白去乙酰化酶的基因,在能量代谢、延缓衰老、抗肿瘤和对抗心脏疾病方面得到关注,更重要的是其对多种神经退行性疾病的作...沉默信息调节因子2同源体1(silent mating type information regulation 2 homolog 1,SIRT1)基因作为一种编码组蛋白去乙酰化酶的基因,在能量代谢、延缓衰老、抗肿瘤和对抗心脏疾病方面得到关注,更重要的是其对多种神经退行性疾病的作用引起了研究人员的兴趣。其激动剂白藜芦醇,是一种天然多酚类物质,也具有神经保护作用,作用途径广泛,如抗氧化,抗缺血等。SRT1720作为新合成的SIRT1激动剂,具有特异性强的优势,但其他方面作用尚待进一步研究。展开更多
文摘目的分析急性脑梗死患者沉默信息调节因子2(silent information regulator 2,SIRT2)与认知功能障碍发生及病情程度的关系。方法回顾性选择2022年5月至2024年5月武汉市第一医院神经内科收治的急性脑梗死合并认知功能障碍患者150例(研究组),研究组依据认知功能障碍严重程度分为轻度组45例、中度组66例和重度组39例。另选取同期武汉市第一医院就诊的急性脑梗死未合并认知功能障碍患者125例(对照组)。采用Spearman相关性分析血清SIRT2水平与认知功能障碍及病情程度的相关性,ROC曲线分析血清SIRT2水平对认知功能障碍及病情的评估价值,并计算曲线下面积(area under curve,AUC)。结果研究组血清SIRT2水平明显高于对照组,差异有统计学意义[(20.38±5.19)mg/L vs(14.66±4.49)mg/L,P<0.05]。重度组血清SIRT2水平明显高于中度组和轻度组,中度组血清SIRT2水平明显高于轻度组,差异有统计学意义(P<0.05)。Spearman相关性分析显示,血清SIRT2水平与认知功能障碍发生及严重程度呈正相关(r=0.510,r=0.527,P<0.01)。ROC曲线分析显示,血清SIRT2水平评估急性脑梗死患者认知功能障碍发生的AUC为0.796(95%CI:0.743~0.842),临界值为19.0 mg/L,敏感性为63.33%,特异性为84.00%;血清SIRT2水平评估急性脑梗死患者认知功能障碍严重程度的AUC为0.747(95%CI:0.655~0.824),临界值为17.2 mg/L,敏感性为75.76%,特异性为71.11%(P<0.05)。结论急性脑梗死患者血清SIRT2水平与认知功能障碍发生及病情密切相关。
基金National Natural Science Foundation of China(81560666)Program for Excellent Young Talents of Zunyi Medical Uiverstity(15zy-002)+1 种基金Science and Technology Innovation Talent Team of Guizhou Province(20154023)the ″Hundred″Level of High-level Innovative Talents in Guizhou Province(QKHRCPT 20165684)；and Program forChangjiang Scholars and Innovative ResearchTeam in University of China(IRT一17R113).
文摘OBJECTIVE To investigate icariside(ICS)Ⅱ protects against PC12 cel damage induced by oxygen-glucose deprivation and reoxygenation and explore its mechanism.METHODS The oxidative stress injury model was induced by oxygen-glucose deprivation/reoxygenation(OGD/R) 2 h/24 h in PC12 cells.N-acetyl-lcysteine(NAC),a classical anti-oxidant,was used as positive control.Pharmacodynamic experimental study groups as follows:control,control+ICS Ⅱ50 μmol·L^(-1),OGD/R,OGD/R+ICSⅡ 12.5 μmol·L^(-1),OGD/R + ICS Ⅱ 25 μmol·L^(-1),OGD/R + ICS Ⅱ50 μmol·L^(-1),and OGD/R+NAC 100 μmol·L^(-1) groups.Cell viability and lactate dehydrogenase(LDH) leakage rate were measured by MTT assay and LDH ELISA kit,respectively.Moreover,reactive oxygen species(ROS) ELISA kit was used for detection of intracellular ROS generation,Mito-SOX fluorescence staining was used for detecting production of ROS in mitochondria and mitochondrial membrane potential(MMP)was detected by rhodamine 123 dye.In addition,PC12 cells apoptosis was detected by one-step TUNEL assay.Furthermore,the expressions of nuclear factor erythroid 2-related factors(Nrf2),Keap1,HO^(-1),NQO^(-1),silent information regulator 3(SIRT3),IDH2,Bax,Bcl-2 and caspase 3 were detected by Western blotting analysis.RESULTS The results of MTT and LDH assay showed that OGD/R reduced the cell viability and improved LDH release compared with the control or ICSⅡ 50 μmol·L^(-1) alone(P<0.01).Meanwhile,OGD/R not only increased intracellular and mitochondrial ROS generation,but also elevated the fluorescence intensity of TUNEL staining,at the same time,the MMP was declined when challenged by OGD/R.Furthermore,the Western blotting results showed that OGD/R induced the increase in the expression of cytoplasm-Nrf2,Keap1,Bax and cleaved-caspase 3 level,while the decrease in the expression of nucleus-Nrf2,HO^(-1),NQO^(-1),SIRT3,IDH2 and Bcl-2(P<0.05).However,ICS Ⅱ significantly increased the viability of PC12 cells and reduced LDH leakage(P<0.01).Notably,ICS Ⅱ also suppressed ROS generation both in the intracellular and mitochondria,as well as restored MMP.It was also worthy to note that ICS Ⅱ decreased the expressions of cytoplasmNrf2,Keap1,Bax and the level of cleaved-caspase3,whereas,it increased the expressions of nucleus-Nrf2,HO^(-1),NQO^(-1),SIRT3,IDH2 and Bcl-2(P<0.05).CONCLUSION ICSⅡ reduced OGD/Rinduced oxidative damage in PC12 cells under the laboratory conditions,and its underlying mechanism may be related to the regulation of Nrf2/SIRT3 signaling pathway.
文摘沉默信息调节因子2同源体1(silent mating type information regulation 2 homolog 1,SIRT1)基因作为一种编码组蛋白去乙酰化酶的基因,在能量代谢、延缓衰老、抗肿瘤和对抗心脏疾病方面得到关注,更重要的是其对多种神经退行性疾病的作用引起了研究人员的兴趣。其激动剂白藜芦醇,是一种天然多酚类物质,也具有神经保护作用,作用途径广泛,如抗氧化,抗缺血等。SRT1720作为新合成的SIRT1激动剂,具有特异性强的优势,但其他方面作用尚待进一步研究。
