Alzheimer’s disease(AD)has become an important public health issue worldwide.p-Coumaric acid(CA)and lactoferrin(Lf)possessed antioxidant,anti-inflammatory,and anti-AD activities.Herein,we hypothesized that a combinat...Alzheimer’s disease(AD)has become an important public health issue worldwide.p-Coumaric acid(CA)and lactoferrin(Lf)possessed antioxidant,anti-inflammatory,and anti-AD activities.Herein,we hypothesized that a combination treatment of CA and Lf would synergistically improve AD symptoms and studied its mechanisms.Twelve-week-old amyloid precursor protein(APP)/presenilin 1(PS1)mice were treated with CA,Lf,or both CA and Lf for 8 weeks.Results showed that individual and combined treatments could ameliorate cognitive deficits to varying degrees,with stronger effects for combined intervention than for CA or Lf alone.Specifically,combined treatment was most effective in improving nesting ability and reducing amyloidββ_(1-42)(Aβ_(1-42))deposition in mice.Moreover,combined treatment was more effective in suppressing APP,β-site APP cleavage enzyme 1,and inflammation;it inhibited the CCAAT-enhancer-binding protein(C/EBPβ)/asparagine endopeptidase(AEP)signaling pathway in the hippocampus and colon and upregulated the expression of tight junction protein zonula occludens-1 in the colon;it also decreased the Firmicutes/Bacteroidetes ratio at the phylum level and increased the relative abundance of Prevotellaceae,Lachnospira,and Eubacterium at the genus level.Overall,the combination of CA and Lf may ameliorate cognitive deficits in APP/PS1 mice by improving inflammation and inhibiting the C/EBPβ/AEP signaling pathway via modulating gut microbiome.展开更多
目的:研究卡托普利对早期高血压大鼠动脉血管平滑肌细胞内质网相关因子葡萄糖调节蛋白78(glucose-regulated protein of 78 kd,GRP78)和C/EBP同源蛋白(CAAT/enhancer binding protein homologous protein,CHOP)表达的影响。方法:将18只...目的:研究卡托普利对早期高血压大鼠动脉血管平滑肌细胞内质网相关因子葡萄糖调节蛋白78(glucose-regulated protein of 78 kd,GRP78)和C/EBP同源蛋白(CAAT/enhancer binding protein homologous protein,CHOP)表达的影响。方法:将18只成年雄性Sprague-Dawley(SD)大鼠随机分为对照组、模型组和卡托普利组(n=6),模型组和卡托普利组均采用大鼠腹主动脉结扎建立高血压大鼠模型。4周后测量血压,应用免疫组化方法检测主动脉血管平滑肌细胞GRP78和CHOP的表达;缺口末端标记法(TUNEL)检测细胞凋亡。结果:(1)模型组平均动脉压(mean arterial blood pressure,MAP)明显增加,卡托普利组血压低于模型组,高于对照组,差异具有统计学意义(P<0.05);(2)模型组内质网因子GRP78、CHOP表达均增加,卡托普利组GRP78、CHOP表达低于模型组,高于对照组,差异具有统计学意义(P<0.01);(3)模型组血管平滑肌细胞凋亡率减少,卡托普利组血管平滑肌细胞凋亡率高于模型组,低于对照组,差异具有统计学意义(P<0.01)。结论:卡托普利可降低高血压大鼠动脉血管平滑肌细胞GRP78和CHOP的表达,增加细胞凋亡。可能与其减弱高血压所致内质网反应,维持血管平滑肌细胞的增殖/凋亡平衡有关。展开更多
基金funded by the National Natural Science Foundation of China(82103818)the Suzhou Applied Basic Research(Medical and Health)Science and Technology Innovation Project(SYW2024179)+1 种基金Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases,Soochow University(KJS2437)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Alzheimer’s disease(AD)has become an important public health issue worldwide.p-Coumaric acid(CA)and lactoferrin(Lf)possessed antioxidant,anti-inflammatory,and anti-AD activities.Herein,we hypothesized that a combination treatment of CA and Lf would synergistically improve AD symptoms and studied its mechanisms.Twelve-week-old amyloid precursor protein(APP)/presenilin 1(PS1)mice were treated with CA,Lf,or both CA and Lf for 8 weeks.Results showed that individual and combined treatments could ameliorate cognitive deficits to varying degrees,with stronger effects for combined intervention than for CA or Lf alone.Specifically,combined treatment was most effective in improving nesting ability and reducing amyloidββ_(1-42)(Aβ_(1-42))deposition in mice.Moreover,combined treatment was more effective in suppressing APP,β-site APP cleavage enzyme 1,and inflammation;it inhibited the CCAAT-enhancer-binding protein(C/EBPβ)/asparagine endopeptidase(AEP)signaling pathway in the hippocampus and colon and upregulated the expression of tight junction protein zonula occludens-1 in the colon;it also decreased the Firmicutes/Bacteroidetes ratio at the phylum level and increased the relative abundance of Prevotellaceae,Lachnospira,and Eubacterium at the genus level.Overall,the combination of CA and Lf may ameliorate cognitive deficits in APP/PS1 mice by improving inflammation and inhibiting the C/EBPβ/AEP signaling pathway via modulating gut microbiome.
文摘目的:研究卡托普利对早期高血压大鼠动脉血管平滑肌细胞内质网相关因子葡萄糖调节蛋白78(glucose-regulated protein of 78 kd,GRP78)和C/EBP同源蛋白(CAAT/enhancer binding protein homologous protein,CHOP)表达的影响。方法:将18只成年雄性Sprague-Dawley(SD)大鼠随机分为对照组、模型组和卡托普利组(n=6),模型组和卡托普利组均采用大鼠腹主动脉结扎建立高血压大鼠模型。4周后测量血压,应用免疫组化方法检测主动脉血管平滑肌细胞GRP78和CHOP的表达;缺口末端标记法(TUNEL)检测细胞凋亡。结果:(1)模型组平均动脉压(mean arterial blood pressure,MAP)明显增加,卡托普利组血压低于模型组,高于对照组,差异具有统计学意义(P<0.05);(2)模型组内质网因子GRP78、CHOP表达均增加,卡托普利组GRP78、CHOP表达低于模型组,高于对照组,差异具有统计学意义(P<0.01);(3)模型组血管平滑肌细胞凋亡率减少,卡托普利组血管平滑肌细胞凋亡率高于模型组,低于对照组,差异具有统计学意义(P<0.01)。结论:卡托普利可降低高血压大鼠动脉血管平滑肌细胞GRP78和CHOP的表达,增加细胞凋亡。可能与其减弱高血压所致内质网反应,维持血管平滑肌细胞的增殖/凋亡平衡有关。
